Cycloheptenopyridine derivatives, process for preparation thereof and antiulcer agents containing the same

ABSTRACT

Provided are cycloheptenopyridine derivatives represented by the general formula ##STR1## [wherein R represents a hydrogen atom or lower alkyl group; R 1  represents a hydrogen atom, halogen atom, lower cycloalkoxy group, amido group, substituted phenoxy group, substituted benzyloxy group, lower alkoxy group optionally containing halogen atoms(s), nitro group, hydroxyl group, lower alkenyloxy group, lower alkylthio group, or a group--NR 4  R 5  (wherein R 4  and R 5  may be the same or different and each represent a hydrogen atom or lower alkyl group, or R 4  and R 5  mutually combine together with the nitrogen atom adjacent thereto to form a 5- or 6-membered heterocyclic group); R 2  represents a hydrogen atom, halogen atom, lower alkyl group optionally containing a halogen atom, lower alkoxy group optionally containing a halogen atom, hydroxyl group, acyl group, lower alkoxycarbonyl group, nitro group or amino group; R 3  represents a hydrogen atom, a lower alkyl group, lower alkoxymethyl group, lower alkylcarbonyl group, lower alkoxycarbonyl group, carbamoyl group, lower alkylcarbamoyl group, lower alkylcarbonylmethyl group, lower alkoxycarbonyl group, lower acyloxymethyl group, lower alkylsulfonyl group, or physiologically acceptable protective group eliminatable in an acid medium or under a physiological condition; n represents 0 or 1; and A represents a methine carbon or nitrogen atom] or their salts. These derivatives and their salts are useful as antiulcer agents.

This invention relates to novel cycloheptenopyridine derivatives usefulas treatment agents for gastric or duodenal ulcer.

As for recent pathophysiological studies of gastric or duodenal ulcer,the behavior of potassium ion-dependent adenosine triphosphatase(hereinafter abbreviated as (H⁺ +K⁺) ATPase), which is involved inhydrochloric acid production in the gastric endoplasmic reticulum,vehicle has drawn attention, and the presence or absence of inhibitoryactivity of this enzyme has come to be used as an indicator forantiulcer agents (Gastroenterology vol. 1, 420, 1943 and ibid vol. 73,921, 1977). It was revealed that this enzyme is located on parietalcells of the gastric mucosa and plays a role of a key enzyme of gastricproton pump, and blockade of this enzyme may be useful to suppressgastric acid secretion. At present, as typical examples of antiulceragents which exhibit selective inhibitory action against this (H⁺ +K⁺)ATPase and are under development, there can be mentioned benzimidazolederivatives such as omeprazole having an unsubstituted or trisubstitutedpyridylmethylsulfinyl group at the side chain (Japanse Laid-Open PatentPublication No. 141783/1979) and NC-1300 having analkylaminophenylmethylsulfinyl group at the side chain (JapaneseLaid-Open Patent Publication No. 60660/1986). Further, it has been knownthat some of the benzimidazole derivatives have a protecting activityfor gastrointestinal mucosal cell (Japanese Laid-Open Patent PublicationNo. 53406/1982).

Histamine H₂ receptor antagonists represented by cimetidine exhibitexcellent healing effect on peptic ulcer because they have a potentinhibitory action on gastric acid secretion. However, it is the presentstate of things that these drugs cannot simply be concluded to besatisfactory drugs because when administration thereof is discontinueddue to complete healing, reccurrence of ulcer is often observed, andthat known (H⁺ +K⁺) ATPase inhibitors represented by omeprazole have aproblem on stability and, therefore, their improvements are beingdesired. Further, peptic ulcers are generally thought to result from animbalance between the aggressive factors such as hydrochloric acid andpepsin and the defensive factors of the tunic mucosa side such as mucoussecretion and mucosal bloodstream, and thus drugs having an inhibitoryaction on a gastric acid secretion and a cytoprotection together arebeing desired.

The present inventors vigorously studied to develop antiulcer agentswhich have a potent inhibitory action on gastric acid secretion and acytoprotection together, and are physiochemically stable and furthercapable of being administered for treatment over a long period. As aresult they have found cycloheptenopyridine derivates having a potentinhibitory action on gastric acid secretion and a cytoprotectiontogether.

Thus, according to this invention are provided cycloheptenopyridinederivatives represented by the general formula ##STR2## [wherein Rrepresents a hydrogen atom or lower alkyl group; R¹ represents ahydrogen atom, halogen atom, lower cycloalkoxy group, amido group,substituted phenoxy group, substituted benzyloxy group, lower alkoxygroup optionally containing halogen atom(s), nitro group, hydroxylgroup, lower alkenyloxy group, lower alkylthio group, or a group--NR⁴ R⁵(wherein R⁴ and R⁵ may be the same or different and each represents ahydrogen atom or lower alkyl group, or R⁴ and R⁵ mutually combinetogether with the nitrogen atom adjacent thereto to form a 5- or 6-membered heterocyclic group; R² represents a hydrogen atom, halogenatom, lower alkyl group optionally containing a halogen atom, loweralkoxy group optionally containing a halogen atom, hydroxyl group, acylgroup, lower alkoxycarbonyl group, nitro group or amino group; R³represents a hydrogen atom, a lower alkyl group, lower alkoxymethylgroup, lower alkylcarbonyl group, lower alkoxycarbonyl group, carbamoylgroup, lower alkylcarbamoyl group, lower alkylcarbonylmethyl group,lower alkoxycarbonylmethyl group, lower acyloxymethyl group, loweralkylsulfonyl group, or physiologically acceptable protective groupeliminatable in an acid medium or under a physiological condition; nrepresents 0 or 1; and A represents a methine carbon or nitrogen atom]or their salts.

Cycloheptenopyridine derivatives represented by the general formula [I]include stereoisomers such as tautomers derived from the partialstructure of benzimidazole, diastereomers derived from the partialstructure of cycloheptenopyridine, enantiomers based on the asymmetriccenter, and the like.

Specific examples of R in the general formula [I] include, for example,a hydrogen atom, a lower alkyl group having 1 to 6 carbon atoms such asmethyl, ethyl, propyl or butyl, etc.

Specific examples of R¹ in the general formula [I] include, for example,a hydrogen atom; a halogen atom such as a chlorine, bromine, iodine orfluorine atom; a lower alkoxy group having 1 to 6 carbon atoms such asmethoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy,tert-butoxy or n-pentoxy; a lower alkenyloxy group such as allyloxy orbutenyloxy; a lower alkoxy group substituted by halogen atom(s) such as2,2,2-trifluoroethoxy or 2,2,3,3,3-pentafluoropropoxy; a lower alkoxygroup substituted by a methoxy, ethoxy or n-propoxy group or the like; alower alkoxy group substituted by a cyclopropoxy, cyclopropylmethyloxy,cyclopentyloxy or cyclohexyloxy group or the like; a lower alkoxy groupcontaining an aromatic ring such as phenyloxy, tolyloxy, pyridyloxy orbenzyloxy; a hydroxyl group; an amino group; a mono- or di-lower (C₁ toC₆) alkylamino group such as methylamino, dimethylamino, ethylamino,diethylamino, isopropylamino, n-propylamino, n-butylamino ortert-butylamino; a cyclic amino group to form a 5- or 6 membered ringsuch as pyrrolidino, piperidino, morpholino, piperazino,N-methylpiperazino or the like; etc.

Specific examples of R² in the general formula [I] include, for example,a hydrogen atom; a halogen atom such as a chlorine, bromine, iodine orfluorine atom; a lower alkyl group having 1 to 6 carbon atoms such asmethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl ortert-butyl; a lower alkoxy group having 1 to 6 carbon atoms such asmethoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy,tert-butoxy or n-pentoxy; a lower alkyl or lower alkoxy groupsubstituted by halogen atom(s) such as trifluoromethyl, 2-fluoroethyl,difluoromethyl, 2,2,2-trifluoroethoxy or 2,2,3,3,3-pentafluoropropoxy; ahydroxyl group; an acyl group having 1 to 6 carbon atoms such as acetyl,propionyl or butyryl; an aroyl group such as benzoyl; a loweralkoxycarbonyl group having 1 to 6 carbon atoms such as methoxycarbonyl,ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl,sec-butoxycarbonyl, tert-butoxycarbonyl or n-pentoxycarbonyl; a nitrogroup; an amino group (including a lower alkylamino group); etc.

Specific examples of R³ in the general formula [I] include, for example,a hydrogen atom; a lower alkyl group having 1 to 6 carbon atoms such asmethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl ortert-butyl; a lower alkoxymethyl group such as methoxymethyl,ethoxymethyl or propoxymethyl; an acyl group having 1 to 6 carbon atomssuch as acetyl, propionyl or butyryl; an aroyl group such as benzoyl; anacyloxymethyl group having 1 to 6 carbon atoms such as acetoxymethyl,propionyloxymethyl or butyryloxymethyl; an aroyloxymethyl group such asbenzoyloxymethyl or toluyloxymethyl; a lower alkoxycarbonyl group having1 to 6 carbon atoms such as methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl,sec-butoxycarbonyl, tert-butoxycarbonyl or n-pentoxycarbonyl; acarbamoyl group, or a carbamoyl group substituted by a lower alkyl grouphaving 1 to 6 carbon atoms such as methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl or tert-butyl; a lower alkylsulfonyl grouphaving 1 to 6 carbon atoms whose lower alkyl moiety is exemplified bymethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl or the like; etc.

As salts of the compounds of the invention are mentionedpharmacologically acceptable addition salts with suitable alkali metalions. Mentioned for example are salts with sodium, potassium, calcium,magnesium, etc.

Compounds [I] are mainly characterized by having a cycloheptenopyridinering, and formation and introduction of this cycloheptenopyridine ringas well as formation and introduction of the benzimidazole ring andimidazopyridine ring can be carried out according to any pertinentsynthetic method.

(a) Formation of the Cycloheptenopyridine Ring

Some of 9-hydroxy-2,3-cycloheptenopyridine derivatives having acycloheptenopyridine ring and represented by the formula [IIa] ##STR3##(wherein R and R¹ are as defined above) are novel substances, and can besynthesized by the synthetic route shown below. ##STR4##

Namely a compound [IIa] can be synthesized by subjecting to a knownoxidation reaction of a substituted or unsubstituted2,3-cycloheptenopyridine derivative (1) either commercially available orsynthesized according to a method disclosed in the literature [YakugakuZasshi (Journal of Pharmacology) 78 268 (1975); J. AM. CHEM. SOC., 79402 (1957); J.C.S., Perkin Transl 1973 (9) 968.], nitrating theresulting 2,3-cycloheptenopyridine derivative (2), subjecting theresulting nitrated compound to substitution reaction(s) to form thecorresponding 4-substituted-2,3-cycloheptenopyridine-N-oxide derivative(4), rearranging the compound (4) with heating in the presence of aceticanhydride, and hydrolyzing the resulting compound with an alkali.

Preparation of the compound (3) from the compound (2) can be carried outby direct nucleophilic substitution of the compound (2). Further, analkoxy derivative or amine derivative can be obtained by firstconverting a compound (2) to the corresponding4-halo-2,3-cycloheptenopyridine-N-oxide derivative and then reacting the4-halo derivative, for example in the presence of a base, either with analcohol such as methanol, ethanol, propanol, allyl alcohol,2,2,2-trifluoroethanol, 2,2,3,3-tetrafluorpropanol, benzyl alcohol ormethoxyethyl alcohol, or with ammonia or an amine such as methylamine,ethylamine, dimethylamine, piperazine, piperidine, pyrrolidine,morpholine or N-methylpiperazine.

This reaction can be carried out in the presence of a base at anappropriate temperature from ice-cooling to the boiling point of thesolvent either using a nucleophilic reagent itself represented by R¹ asa solvent or using an organic solvent such as tetrahydrofuran, dioxane,acetone, acetonitrile, N,N-dimethylformamide or hexamethyl phosphorictriamide. When an amine derivative is obtained, the reaction is carriedout, preferably in a sealed tube, for about 1 to 48 hours. Examples ofbases used in this reaction include alkali metals such as sodium,potassium and lithium; alkali metal hydrides such as sodium hydride andpotassium hydride; alcoholates such as potassium t-butylate and sodiummethylate; alkali metal hydroxides such as lithium hydroxide, sodiumhydroxide and potassium hydroxide; and alkali metal carbonates such assodium hydrogen carbonate and potassium hydrogen carbonate. Theresulting compound (4) is heated (80° to 150° C.) in the presence ofacetic anydride alone or sulfuric acid or perchloric acid or the like togive the corresponding 9-acetoxy-2,3-cycloheptenopyridine derivative(5), which is then hydrolyzed in the presence of a base, for example, analkali metal hydroxide such as sodium hydroxide or potassium hydroxide,or an alkali metal carbonate such as sodium hydrogen carbonate orpotassium hydrogen carbonate, whereby the corresponding compound [IIa]can be prepared. Examples of the solvent used include methanol, ethanol,water, etc. The reaction is usually completed in 10 minutes to 2 hoursat a temperature of room temperature to the boiling point of thesolvent.

(b) Synthesis of Compounds [I]

Compounds of the formula [I] can be synthesized according to variousmethods. For example, a reactive derivative represented by the generalformula ##STR5## (wherein X represents a halogen atom, or analkylsulfonyl or arylsulfonyl group, and R and R¹ are as defined above)is reacted with a 2-mercaptobenzimidazole or2-mercapto[4,5-b]imidazopyridine derivative represented by the generalformula ##STR6## (wherein R², R³ and A are as defined above) or a saltthereof to prepare a sulfide type compound [Ib] where n in the generalformula [1] expresses zero. ##STR7##

A reactive derivative [II] can be obtained either by reacting a compound[IIa] with a halide such as thionyl chloride, phosphorus oxychloride,phosphorus trichloride, phosphorus tribromide, p-toluenesulfonylchloride or the like, or by reacting an aforementioned compound (4) witha halogenating reagent such as thionyl chloride, phosphorus oxychloride,phosphorus trichloride, p-toluenesulfonyl chloride or1,3,5-trichlorocyanuric acid.

A sulfide type compound [Ib] can also be obtained by reacting a reactivederivative [II] with a 2-mercaptobenzimidazole derivative or2-mercapto[4,5-b]imidzaopyridine derivative represented by the generalformula ##STR8## (wherein R² and A are as defined above) or a saltthereof to obtain a compound of the general formula ##STR9## and then,if desired, subjecting the compound [Ia] to a known N-alkylationreaction, N-acylation reaction or N-sulfonylation reaction.

Specific examples of X in the reactive derivative [II] include, forexample, halogen atoms such as chlorine, bromine and iodine atoms; loweralkylsulfonyloxy groups such as methanesulfonyloxy andethanesulfonyloxy; arylsulfonyloxy groups such as benzenesulfonyloxy andp-toluenesulfonyloxy; etc. Examples of the salts of the compounds [III]and [IIIa] include salts with alkali metals such as sodium andpotassium.

The reaction to condense a reactive derivative [II] with a compound[III] or [IIIa] is preferably carried out in a hydrophilic organicsolvent such as methanol, ethanol, acetone, tetrahydrofuran,N,N-dimethylformamide or dimethylsulfoxide or in a mixed solvent of sucha solvent and water. The reaction temperature is in the range of 0° to150° C., preferably 80° to 100° C., and it is preferred that thereaction is carried out in the presence of a base.

Examples of the base include alkali metal hydroxides such as sodiumhydroxide and potassium hydroxide; alkali metal carbonates such assodium carbonate, potassium carbonate, sodium hydrogen carbonate andpotassium hydrogen carbonate; organic amines such as triethylamine,pyridine and N,N-dimethylaniline; etc. The reaction is usually completedin 3 to 12 hours.

After completion of the reaction, the reaction solution is subjected toconventional methods, for example, the usually adopted means such asextraction, recrystallization and chromatography to obtain the compound[Ia] or [Ib].

Further, a sulfoxide type compound [Ic] which corresponds to a compoundof the general formula [I] wherein n is 1 can be prepared by oxidizing acompound [Ia] or [Ib] or a salt thereof. ##STR10##

The oxidation reaction of a compound [Ia] or [Ib] can be carried out inbenzene, chloroform, methylene chloride, methyl acetate, ethyl acetate,acetonitrile, methanol, N,N-dimethylformamide, N,N-dimethylacetamide,acetic acid, formic acid, water or another solvent or a mixed solventthereof using an equivalent amount of an oxidizing agent. Usually, thereaction is carried out at -30° C. to room temperature and completed in5 minutes to 2 hours. As examples of the oxidizing agent are mentionedoxidizing agents usually used for oxidation of sulfides such asperacetic acid, hydrogen peroxide, trifluoroperacetic acid,m-chloroperacetic acid and sodium metaperiodate. After completion of thereaction the compound [Ic] can be obtained from the reaction solution byconventional methods, for example, by usual separation and purificationmeans such as extraction, recrystallization and chromatography.

The inhibitory action on gastric acid secretion and cytoprotection ofthe following compounds, which are representative examples of compounds[I] of the invention, are detailedly described below:

9-(5-Methoxybenzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridine(compound of Example 63),

9-(Benzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridine sodiumsalt (compound of Example 68),

9-(5-Methylbenzimidazole-2-yl)sulfinyl-2,3-cycloheptenopyridine(compound of Example 75),

9-(Benzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridine(compound of Example 77),

9-(5-Fluorobenzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridine(compound of Example 78),

9-(Benzimidazole-2-yl)sulfinyl-4-(2-methoxyethoxy)-2,3-cycloheptenopyridine(compound of Example 96), and

9-(Benzimidazole-2-yl)sulfinyl-4-methoxy-3-methyl-2,3-cycloheptenopyridine(compound of Example 109)

(a) Inhibitory Effect on Gastric Acid Secretion in Ghosh-Schild Rats

Each of male Wistar-KV rats was fasted for 24 hours, and a tracheacannula was set up under urethane anesthesia. The abdomen was incised, adouble cannula was set up at the forestomach, and then the abdomen wasclosed. The gastric acid secretion was stimulated by intravenousinfusion of 10 μg/kg/hr. Physiological saline was perfused into thestomach through the double cannula at a rate of 1 ml/min., and theeffluent was collected every 10 minutes. The acidity of the effluent wasmeasured, using an automatic titrator, by titrating the effluent with1/100N sodium hydroxide to pH 7. When the acid secretion had reached astable plateau, the test drug was intravenously administered, and thegastric acid secretion was measured 3 hours after the test drugadministration. The antisecretory effect was expressed as percentages ofthe secretory amount before administration of the test compound. Theresults are shown in Table-1.

(b) Inhibitory Effect on Formation of Gastric Lesion Induced by Ethanol

Male Wistar rats weighing 170 to 270 g were used. Each of the rats wasplaced in separate cages to deprive of food but allowed free access towater for 4 hours. Test drugs or the control drug were orallyadministered respectively in amounts of 3, 10 and 30 mg/kg, and 30minutes thereafter 1 ml of 99.5% ethanol were orally administeredrespectively. One hour after the ethanol administration the rats weresacrificed by cervical vertebrae dislocation, and the stomachs wereremoved with 8 ml of 1% formalin and put into 1% formalin for 30 minutesto fix the gastric wall. After the fixing, each stomach was opened alongthe greater curvature, and then after the mucosal surface was washedwith tap water, the total length lesions generated at the glandubportion was determined as an ulcer index.

The antiulcer effect by the test drug was expressed by the ED50 value(the dose of the test compound to inhibit the ulcer by 50% to the ulcerindex of the non-treated group). The results are shown in Table-2. Onlythe solvent was administered to the non-treated group.

                  TABLE 1                                                         ______________________________________                                                       Inhibiting action of gastric                                                  acid secretion (rat i.v.)                                      Example No.      3 mg/kg  1 mg/kg                                             ______________________________________                                        63               73.8%    45.7%                                               68               --       54.9%                                               75               42.1%    --                                                  77               74.7%    44.7%                                               78               82.9%    65.4%                                               96               57.4%    38.6%                                               109              77.6%    --                                                  Omeprazole       --       36.9%                                               (Control drug)                                                                ______________________________________                                    

Inhibition percentages at 180 minutes after the administrations areshown.

                  TABLE 2                                                         ______________________________________                                        Example No.   ED.sub.50 value (mg/kg P.O)                                     ______________________________________                                        77            13.0                                                            68            10.9                                                            ______________________________________                                    

As apparent from the above test results, compounds [I] are potenttreatment drugs for gastric or duodenal ulcer.

An antiulcer agent containing as an active ingredient a compound of theformula [I] or a salt thereof can mainly be orally or parenterallyadministered (for example, administered by intramuscular injection,intravenous injection, subcutaneous administration, rectaladministration, transcutaneous administration, or the like), andpreferably can be orally administered. Various and various drug formssuitable for the respective administrations can be adopted. As for solidformulations, a compound [I] can be formulated into tablets, capsules,granules, powders or fine granules, and can also be formulated inenteric coated agents by a coating technique therefor. Further, a liquidagent can be prepared by converting a compound [I] to an alkali salt orphysiologically acceptable salt, and then dissolving the salt in wateror an aqueous alkali solution.

Although the dose of a compound [I] to patients is varied depending onthe age, the condition of the disease and the like, it is generallypreferred to administer it to an adult in an amount of 0.5 to 1,000 mg,particularly 1 to 200 mg, divided into 1 to 3 times, per day.

Syntheses of starting compounds used in the invention and compounds [I]of the invention are more specifically and detailedly described belowaccording to reference examples and examples, but the invention shouldnot be limited thereto.

REFERENCE EXAMPLE 1 2,3-Cycloheptenopyridine-N-oxide

1) 14.72 g (0.1 mol) of 2,3-Cycloheptenopyridine is dissolved in 150 mlof dichloromethane, 21.57 g (0.1 mol) of m-chloroperbezoic acid is addedby portions under ice cooling and stirring, and the mixture is stirredat the same temperature for 3 hours. After the reaction, 150 ml of asaturated aqueous sodium hydrogen carbonate solution is added, followedby extraction with methylene chloride. The methylene chloride layer issufficiently washed with a saturated aqueous sodium hydrogen carbonatesolution and saturated saline, and dried over anhydrous magnesiumsulfate, and the solvent is distilled away under reduced pressure. Theresulting solid residue is recrystallized from ether-n-hexane to obtain14.13 g (86.6 %) of 2,3-cycloheptenopyridine-N-oxide as grayish whitecrystals having a melting point of 107° to 109° C.

IRν max(KBr): 3080, 2924, 1610, 1432, 1268, 1246, 810 cm⁻¹.

NMR(CDCl₃)δ: 1.09-2.03(6H,m), 2.57-2.91 (2H,m), 3.18-3.50(2H,m),6.68-7.03(2H,m), 7.92-8.23(1H,m).

2) 14.72 g (0.1 mol) of 2,3-cycloheptenopyridine is dissolved in 100 mlof acetic acid, and 13.3 ml of 30 % aqueous hydrogen oxide is added,followed by 8 hour stirring with heating at 100° C. 7.4 ml of 30%Aqueous hydrogen oxide is further added, and then after 8 hour stirringwith heating, the solvent is distilled away under reduced pressure. Theresulting residue is extracted with chloroform, and the extract issufficiently washed with a saturated aqueous sodium hydrogen carbonatesolution and saturated saline and dried over anhydrous magnesiumsulfate. Then, the solvent is distilled away under reduced pressure toobtain almost quantitatively 2,3-cycloheptenopyridine-N-oxide.

REFERENCE EXAMPLE 2 4-Nitro-2,3-cycloheptenopyridine-N-oxide

3.92 g (24 mmoles) of 2,3-cycloheptenopyridine-N-oxide is dissolved in15 ml of sulfuric acid under ice cooling, and the solution is stirredfor 40 minutes with heating at 85° to 90° C., while 13 ml of fumingnitric acid is added dropwise thereto. After the reaction, ice water isadded, and after neutralization with a 40% aqueous sodium hydroxidesolution, the mixture is extracted with methylene chloride. Themethylene chloride layer is washed with saturated saline and dried overanhydrous magnesium sulfate, and the solvent is distilled away underreduced pressure to obtain 2.23 g (44.6%) of4-nitro-2,3-cycloheptenopyridine-N-oxide as yellowish crystals having amelting point of 118° to 120° C.

IRν max(KBr): 3110, 2928, 2852, 1529, 1570, 1516, 1422, 1340, 1272,1144, 828, 700 cm⁻¹.

NMR(CDCl₃)δ: 1.54-2.08(6H,m), 2.85-3.17 (2H,m), 3.27-3.63(2H,m), 7.46(1H,d,J=8 Hz), 8.11(1H,d,J=8 Hz).

REFERENCE EXAMPLE 3 4-chloro-2,3-cycloheptenopyridine-N-oxide

2.23 g (10.7 mmol) of 4-Nitro-2,3-cycloheptenopyridine-N-oxide is addedby portions to 7.85 g (0.1 mol) of acetyl chloride under ice cooling andstirring, and the mixture is stirred at the same temperature for 1 hour.After the reaction, the mixture is poured into ice water, followed byextraction with ethyl acetate. The ethyl acetate layer is washed withsaturated saline and dried over anhydrous magnesium sulfate, and thesolvent is distilled away under reduced pressure. The resulting residueis purified by silica gel column chromatography (chloroform-methanol95:5) and recrystallized from ether-n-hexane to obtain 1.77 g (83.9%) of4-chloro-2,3-cycloheptenopyridine-N-oxide as yellowish prismaticcrystals having a melting point of 117° to 118° C.

IRν max(KBr): 3112, 2924, 2848, 1438, 1418, 1336, 1256, 1170, 1110, 830,710 cm⁻¹.

NMR(CDCl₃)δ: 1.50-2.05(6H,m), 2.80-3.15 (2H,m), 3.22-3.55(2H,m), 7.03(1H,d,J=8 Hz), 7.99(2H,d,J=8 Hz).

REFERENCE EXAMPLE 4 4-Methoxy-2,3-cycloheptenopyridine-N-oxide

810 mg (3.89 mmol) of 4-mitro-2,3-cycloheptenopyridine-N-oxide isdissolved in 10 ml of methanol, 250 mg of sodium hydroxide is addedthereto, and the mixture is refluxed for 45 minutes. After cooling themethanol is distilled away under reduced pressure, the resulting residueis extracted with chloroform. The chloroform layer is washed withsaturated saline and dried over anhydrous magnesium sulfate, and thesolvent is distilled away under reduced pressure. The resulting residueis purified by silica gel column chromatography (chloroform-methanol95:5) and recrystallized from ethyl acetate to obtain 710 mg (94.5%) of4-methoxy-2,3-cycloheptenopyridine-N-oxide as yellowish prismaticcrystals having a melting point of 148° to 149° C.

IRν max (KBr): 3075, 2916, 2848, 1615, 1570, 1460, 1428, 1344, 1284,1242, 1188, 1034, 828, 746 cm⁻¹.

NMR(CDCl₃)δ: 1.43-2.04(6H,m), 2.65-2.97(2H,m), 3.20-3.54(2H,m),3.83(3H,s), 6.57(1H,d,J=8 Hz), 8.08(1H,d,J=8 Hz).

REFERENCE EXAMPLE 5

4-(3-Methoxypropoxy)-2,3-cycloheptenopyridine-N-oxide

1.28 g (14.2 mmol) of 1-methoxypropanol is dissolved in 7 ml ofdimethylsulfoxide (DMSO) in an argon stream, 566 mg (14.2 mmol) of 60%sodium hydride is added thereto, and the mixture is stirred at 60° C.for 30 minutes. Under stirring at room temperature, 1.40 g (7.08 mmol)of 4-chloro-2,3-cycloheptenopyridine-N-oxide dissolved in 5 ml of DMSOis added dropwise, followed by stirring at 40° C. for 1 hour.Thereafter, with stirring at room temperature, 566 mg (14.2 mmol) of 60%sodium hydride and 310 mg (3.44 mmol) of 1-methoxypropanol are addded,and the mixture is stirred at 40° C. for 16 hours. After cooling thereaction mixture is poured in ice-saline, followed by extraction withchloroform. The chloroform layer is washed with saturated saline anddried over anhydrous magnesium sulfate, and the solvent is distilledaway under reduced pressure. The resulting residue is purified by silicagel column chromatography (chloroform-methanol 40:1) to obtain 1.15 g(64.5%) of 4-(3-methoxypropoxy)-2,3-cycloheptenopyridine-N-oxide as apale brown oily substance.

IRν max(Neat): 2948, 2856, 1450, 1342, 1288, 1240, 1200, 1188, 1136,1120, 1092, 1064, 1028, 750, 662 cm⁻¹.

NMR(CDCl₃)δ: 1.40-2.00(6H,m) 2.04(2H,t, J=6 Hz), 2.63-2.94(2H,m), 3.31(3H,s), 3.20-3.65(4H,m), 4.04 (2H,t,J=7 Hz), 6.57(1H,d,j=7 Hz),8.03(1H,d,J=7 Hz).

REFERENCE EXAMPLE 64-(2-benzyloxyethoxy)-2,3-cycloheptenopyridine-N-oxide

In a stream of argon, 804 mg (20.1 mmol) of 60% sodium hydride issuspended in 7 ml of DMSO, 2.86 ml (20.1 mmol) of 2-benzyloxyethanol isadded dropwise with stirring at room temperature, and the mixture isstirred at 60° C. for 35 minutes. Further, 1.40 g (7.05 mmol) of4-chloro-2,3-cycloheptenopyridine-N-oxide dissolved in 5 ml of DMSO isadded dropwise thereto with stirring at room temperature, and themixture is stirred at 40° C. for 3 hours and 20 minutes. After cooling,the reaction mixture is poured in ice water, followed by extraction withmethylene chloride. The methylene chloride layer is washed successivelywith water and saturated saline and dried over anhydrous magnesiumsulfate, and the solvent is distilled away under reduced pressure. Theresulting residue is purified by silica gel column chromatography(chloroform-methanol 40:1) to obtain 2.12 g (96.1%) of4-(2-benzyloxyethoxy)-2,3-cycloheptenopyridine-N-oxide as a pale brownoily substance.

IRν max(Neat): 2924 2852, 1444, 1342, 1290, 1242, 1200, 1166, 1134,1092, 1068, 1034, 892, 758, 744, 690 cm⁻¹.

NMR(CDCl₃)δ: 1.43-2.05(6H,m), 2.70-3.00 (2H,m), 3.25-3.55(2H,m),3.70-3.96(2H,m), 4.00-4.24(2H,m), 4.60(2H,s), 6.58(1H,d,J=8 Hz),7.30(5H,bs), 8.04(1H,d,J=8 Hz).

REFERENCE EXAMPLE 7 4-(2-Hydroxyethoxy)-2,3-cycloheptenopyridine-N-oxide

In a stream of argon, 1.63 g (70.0 milligram atoms) of metal sodium isadded by portions to 28 ml of ethylene glycol under ice cooling andstirring, and the mixture is stirred for 1 hour with heating at 100° C.Then, 7.00 g (35.0 mmol) of 4-chloro-2,3-cycloheptenopyridine-N-oxide isadded with stirring at room temperature, and the mixture is stirred at120° C. for 3 hours and 30 minutes. After the reaction, the mixture ispoured in ice water, followed by extraction with chloroform. Thechloroform layer is dried over anhydrous magnesium sulfate, and thesolvent is distilled away under reduced pressure. The resulting residueis crystallized from ethanol-ether to give 3.09 g (38.9%) of4-(2-hydroxyethoxy)-2,3-cycloheptenopyridine-N-oxide as colorless pillarcrystals having a melting point of 159°-160° C. The mother liquor isconcentrated, and the residue is purified by silica gel columnchromatography (chloroform-methanol 20:1→15:1→10:1) to give 2.62 g(33.4% of the desired substance (total yield 72.3%).

IRν max(KBr): 3224, 3104, 2912, 2852, 1450, 1344, 1292, 1236, 1204,1186, 1138, 1092, 1062, 1032, 890, 822, 758 cm⁻¹.

NMR(CDCl₃)δ: 1.35-2.10(6H,m), 2.65-3.03(2H,m), 3.22-3.55(2H,m),3.55-4.15(5H,m), 6.57(1H,d,J=7 Hz), 7.97(1H,d,J=7 Hz).

REFERENCE EXAMPLE 8 4-(2-Chloroethoxy)-2,3-cycloheptenopyridine-N-oxide

In a stream of argon, 2.23 g (10.0 mmol) of4-(2-hydroxyethoxy)-2,3-cycloheptenopyridine-N-oxide is dissolved in 22ml of chloroform, 1.97 ml (27.0 mmol) of thionyl chloride is addeddropwise thereto with stirring at -12° C., and the mixture is stirred atroom temperature for hours and 20 minutes and then stirred at 60° C. for1 hour and 15 minutes. After cooling, the reaction mixture is pouredinto ice--a saturated aqueous sodium hydrogen carbonate solution,followed by extraction with chloroform. The chloroform layer is washedsuccessively with a saturated aqueous sodium hydrogen carbonate solutionand water and dried over anhydrous magnesium sulfate, and then thesolvent is distilled away under reduced pressure. The resulting residueis purified by silica gel column chromatography (chloroform-methanol20:1) to give 2.15 g (89.1%) of4-(2-chloroethoxy)-2,3-cycloheptenopyridine-N-oxide as colorless needlecrystals having a melting point of 109° to 110.5° C.

IRν max(KBr): 2924 2852, 1448, 1292, 1240, 1200, 1190, 1068, 1032, 824,814, 774 cm⁻¹.

NMR(CDCl₃)δ: 1.39-2.01(6H,m), 2.66-3.00 (2H,m), 3.20-3.53(2H,m), 3.80(2H,t,J=6 Hz), 6.55(1H,d,J=8 Hz), 8.05(1H,d,J=8 Hz).

REFERENCE EXAMPLE 94-[2-(2-pyridylmethoxy)ethoxy]-2,3-cycloheptenopyridine-N-oxide

In a stream of ar9on, 2.23 9 (10.0 mmol) of4-(2-hydroxyethoxy)-2,3-cycloheptenopyridine-N-oxide is suspended in 30ml of tetrahydrofuran (THF), 600 mg (15.0 mmol) of 60% sodium hydride isadded by portions thereto under ice cooling and stirring, and themixture is stirred at room temperature for 10 minutes. Then, after 20minutes stirring at 50° C., 1.65 g (12.90 mmol) of picolyl chloridedissolved in 15 ml of THF is added dropwise thereto with stirring atroom temperature, and the mixture is stirred at 90° C. for 8 hours.Then, after 12 hours stirring at room temperature, 200 mg (5 mmol) of60% sodium hydride is added, and the mixture is refluxed with heatingfor 3 hours. After the reaction, the solvent is distilled away underreduced pressure, the risidue is addd to ice water, and the mixture isextracted with methylene chloride. The methylene chloride layer is driedover anhydrous magnesium sulfate, and the solvent distilled away underreduced pressure. The resulting residue is purified by silica gel columnchromatography (chloroform-methanol 30:1→10:1) to give 2.33 g (74.2%) of4-[2-(2-pyridylmethoxy)ethoxy]-2,3-cycloheptenopyridine-N-oxide as abrown oily substance.

IRν max(Neat): 2924 2852, 1590, 1446, 1342, 1290, 1240, 1200, 1134,1092, 1064, 1036, 892, 758 cm⁻¹.

NMR(CDCl₃)δ: 1.37-2.02(6H,m), 2.70-3.02 (2H,m), 3.21-3.51(2H,m),3.80-4.03(2H,m), 4.05-4.31(2H,m), 6.59(1H,d,J=8 Hz), 7.03-7.78 (3H,m),8.04(1H,d,J=8 Hz), 8.51 (1H,d,J=8 Hz).

REFERENCE EXAMPLE 104-[2-(2-oxopyrrolidin-1-yl)ethoxy]-2,3-cycloheptenopyridine-N-oxide

In a stream of argon, 632 mg (15.8 mmol) of 60% sodium hydride issuspended in 30 ml of dimethylformamide (DMF), 1.12 g (13.1 mmol) of2-pyrrolidone is added thereto under ice cooling, and the mixture isstirred at 80° C. for 1 hour and 30 minutes. Then, under stirring atroom temperature, 2.11 g (8.73 mmol) of4-(2-chloroethoxy)-2,3-cycloheptenopyridine-N-oxide dissolved in 15 mlof DMF is added dropwise, and the mixture is stirred at 60° C. for 2hours and 10 minutes. After cooling, the mixture is poured into asaturated aqueous sodium hydrogen carbonate solution, followed byextraction with methylene chloride. The methylene chloride layer isdried over anhydrous magnesium sulfate, and the solvent is distilledaway under reduced pressure. The resulting residue is subjected toseparation and purification by silica gel column chromatography(chloroform-methanol 20:1→10:1→4:1) to obtain 334 mg (53.3%) of4-[2-(2-oxypyrrolidin- 1-yl)ethoxy]-2,3-cycloheptenopyridine-N-oxide ascolorless powder having a melting point of 112° to 115° C.

IRν max(KBr): 2924, 1672, 1452, 1344, 1292, 1240, 1202, 1188, 1138,1092, 1068, 1028, 886, 832, 758 cm¹.

NMR(CDCl₃)δ: 1.40-2.56(10H,m), 2.65-3.00 (2H,m), 3.25-3.62(4H,m), 3.68(2H,t,J=6 Hz), 4.09(2H,t,J=6 Hz), 6.55(1H,d,J=8 Hz), 8.04(1H,d,J =8 Hz)

REFERENCE EXAMPLE 11 4-Ethoxy-3-methyl-2,3-cycloheptenopyridine-N-oxide

1.00 g (4.50 mmol) of 4-nitro-3-methyl-2,3-cycloheptenopyridine-N-oxideis dissolved in 15 ml of ethanol, 540 mg (13.5 mmol) of sodium hydroxideis added thereto under ice cooling and stirring, and after stirring atroom temperature for 19 hours, the mixture is refluxed with heating for30 minutes. Ater cooling, the ethanol is distilled away under reducedpressure and the resulting residue is extracted with chloroform. Thechloroform layer is washed successively with water and saturated salineand dried over anhydrous magnesium sulfate, and the solvent is distilledaway under reduced pressure. The resulting residue is purified by silicagel column chromatography (chloroform-methanol 40:1) to obtain 679 mg(68.2%) of 4-ethoxy-3-methyl-2,3-cycloheptenopyridine-N-oxide as palebrown powder having a melting point of 107° to 108° C.

IRν max(KBr): 2976, 2932, 2852, 1478, 1454, 1420, 1388, 1332, 1248,1228, 1192, 1168, 1136, 1052, 1026, 966, 928, 868 cm⁻¹.

NMR(CDCl₃)δ: 1.42(3H,t,J=7 Hz), 1.50-2.03 (6H,m), 2.16(3H,s), 2.65-3.93(2H,m), 3.23-3.48(2H,m), 3.81 (2H,q,J=7 Hz), 7.95(1H,s).

Compounds shown in Table-3 are obtained in the same manner as Referenceexamples 1 to 11.

                                      TABLE 3                                     __________________________________________________________________________     ##STR11##                                                                    Reference                                                                     Example              Melting point                                            No.   R   R.sup.1    (yield)                                                                              IRνcm.sup.-1                                                                             NMR(CDCl.sub.3)δ              __________________________________________________________________________    12    H   OCH.sub.2 CH.sub.2 OCH.sub.3                                                             Palely brown                                                                         (KBr) 3016, 2980, 2920, 2872,                                                               1.41-2.00(6H, m), 2.66-3.03(2H,                                               b,                                                       pillar crystal                                                                       2852, 1454, 1292, 1240, 1202,                                                               J=10Hz), 3.41(5H, bs),                                                        3.58-3.86                                                (56.0%)                                                                              1190, 1136, 1120, 1092, 1064,                                                               (2H, m), 3.96-4.30(2H, m),                                                    6.57(1H,                                                 71-73° C.                                                                     1034, 760,    d, J=8Hz), 8.03(1H, d, J=8Hz)       13    H   OCH.sub.2 CH.sub.2CH.sub.2                                                               Colorless                                                                            (KBr) 2916, 1448, 1422, 1344,                                                               1.40-2.03(6H, m), 2.70-3.30(2H,                                               m),                                                      amorphous                                                                            1292, 1238, 1204, 1188, 1138,                                                               3.20-3.55(2H, m), 4.52(2H, d,                                                 J=5Hz),                                                  powder 1062, 1028, 1000, 924, 884,                                                                 5.10-5.58(2H, m), 5.76-6.23                              (50.9%)                                                                              826, 810, 766, 744,                                                                         (1H, m), 6.56(1H, d, J=7Hz),                                                  8.03                                                     149-150° C.   (1H, d, J=7Hz)                      14    H   OCH.sub.2 CF.sub.3                                                                       Colorless                                                                            (KBr) 2920, 2944, 1454, 1296,                                                               1.40-2.17(6H, m), 2.60-3.04(2H,                                               m),                                                      needle crystal                                                                       1274, 1240, 1202, 1174, 1160,                                                               3.16-3.56(2H, m), 4.35(2H, q,                                                 J=8Hz,                                                   (48.6%)                                                                              1134, 1098, 1038, 972, 862,                                                                 16Hz), 6.55(1H, d, J=8Hz),                                                    8.07                                                     166-169° C.                                                                   764,          (1H, d, J=8Hz)                      15    H   OCH.sub.2 CF.sub.2 CF.sub.3                                                              Colorless                                                                            (KBr) 2940, 1454, 1346, 1298,                                                               1.45-2.05(6H, m), 2.70-2.97(2H,                                               m),                                                      prismatic                                                                            1272, 1240, 1216, 1188, 1136,                                                               3.25-3.50(2H, m), 4.40(2H, t,                                                 J=12Hz),                                                 crystal                                                                              1110, 1094, 1068, 1040, 1026,                                                               6.55(1H, d, J=5Hz), 8.08                                 (72.8%)                                                                              956, 810, 764,                                                                              (1H, d, J=5Hz)                                           135-138° C.                                       16    H   OCH.sub.2 CF.sub.2 CHF.sub.3                                                             Colorless                                                                            (KBr) 2936, 1478, 1452, 1346,                                                               1.45-2.05(6H, m), 2.68-2.95(2H,                                               m),                                                      powder 1296, 1270, 1240, 1200, 1136,                                                               3.25-3.50(2H, m), 4.35(2H, t,                                                 J=12Hz),                                                 (60.0%)                                                                              1098, 1068, 1036, 962, 950,                                                                 5.36, 5.96, 6.52(1H,                                                          t×3,                                               106.5-108° C.                                                                 886, 840, 832, 810, 768,                                                                    J=3Hz), 6.57(1H, d, J=6Hz),                                                   8.07                                                                          (1H, d, J=6Hz)                      17    H   O(CH.sub.2).sub.2 OPh                                                                    Palely brown                                                                         (KBr) 2924, 1490, 1452, 1438,                                                               1.38-2.03(6H, m), 2.66-2.93(2H,                                               m),                                                      powder 1282, 1236, 1198, 1180, 1134,                                                               3.25-3.55(2H, m), 4.29(4H, s),                           (70.5%)                                                                              1086, 1068, 930, 896, 832,                                                                  6.62(1H, d, J=7Hz), 6.74-7.40                            149.5-152° c.                                                                 760,          (5H, m), 8.05(1H, d, J=7Hz)         18    H                                                                                  ##STR12## Colorless powder (62.0%) 152-153° C.                                          (KBr) 2956, 2916, 2852, 1446, 1346, 1264,                                     1246, 1190, 1136, 1112, 1064, 1006, 988, 932,                                 90, 874, 856, 732,                                                                          1.50-2.49(6H, m), 2.70-3.23(6H,                                               m), 3.23-3.65(2H, m),                                                         3.72-4.00(4H, m), 6.67(1H, d,                                                 J=6Hz), 8.05(1H, d, J=6Hz)          19    H   SCH.sub.2 CH.sub.2 CH.sub.3                                                              Colorless                                                                            (KBr) 3432, 3068, 2960, 2924,                                                               106(3H, t, J=6Hz), 1.46-2.03                             amorphous                                                                            2848, 2824, 1426, 1336, 1268,                                                               (8H, m), 2.52-3.15(4H,                                                        m)3.20-3.52                                              powder 1242, 1214, 1194, 1130, 1090,                                                               (2H, m), 6.87(1H, d, J=6Hz),                                                  8.02                                                     (79.6%)                                                                              1038, 1000, 880, 828, 742,                                                                  (1H, d, J=6Hz)                                           --     700, 634, 556,                                    20    3-CH.sub.3                                                                        4-OCH.sub.2 CF.sub.2 CF.sub.2 H                                                          Palely brown                                                                         (neat) 2932, 1455, 1419, 1296,                                                              1.50-2.01(6H, m), 2.19(2H, s),                           oily   1272, 1248, 1224, 1197, 1170,                                                               2.69-2.95(2H, m), 3.20-3.50(2H,                                               m),                                                      substance                                                                            1110, 1068, 1050, 1032, 753,                                                                4.11(2H, t, J=12Hz), 5.46,                                                    6.05,                                                    (100%)               6.63(1H, t×3, J=4Hz),                                                   7.98(1H, s)                                              --                                                       21    H   OEt        Palely brown                                                                         (KBr) 3320, 2924, 1448, 1290,                                                               1.30-1.96(6H, m), 1.43(3H, t,                                                 J=7.5Hz),                                                powder 1236, 1190, 1138, 1116, 1066,                                                               2.69-2.96(2H, m),                                                             3.26-3.53(2H,                                            (74.3%)                                                                              1038, 894,    m), 4.02(2H, q, J=7.5Hz),                                                     6.53(1H, d,                                              148-149.5° C. J=9Hz), 8.04(1H, d, J=9Hz)          22    H   O-n-BU     Paleley brown                                                                        (KBr) 3384, 2952, 2920, 2852,                                                               0.96(3H, t, J=7.5Hz),                                                         1.16-2.35                                                amorphous                                                                            1450, 1406, 1290, 1240, 1198,                                                               (10H, m), 2.73-3.05(2H, m),                              powder 1188,         3.18-3.56(2H, m), 3.94(2H, t,                                                 J=7.5Hz),                                                (54.8%)              6.53(1H, d, J=9Hz), 8.03(1H, d,                                               J=9Hz)                                                   --                                                       23    H                                                                                  ##STR13## Palely brown oily substance (72.5%) --                                               (neat) 3032, 2924, 1604, 1506, 1442, 1270,                                    1246, 1198, 1166,                                                                           1.33-2.20(6H, m), 2.32(3H, s),                                                2.73-3.06(2H, m), 3.28-3.56(2H,                                               m), 6.43(1H, d, J=9Hz),                                                       6.81(2H, d, J=10.5Hz), 7.15(2H,                                               d, J=10.5Hz), 7.96(1H, d,                                                     J=9Hz)                              24    H                                                                                  ##STR14## Palely brown amorphous powder (92.6%) --                                             (KBr) 3068, 2976, 2924, 1612, 1450, 1412,                                     1342, 1292, 1138, 1062, 1028,                                                               0.19-0.81(4H, m), 1.03-1.36(1H,                                               m), 1.40-2.06(6H, m),                                                         2.71-3.03(2H, m), 3.24-3.58(2H,                                               m), 3.80(2H, d, J=7.5Hz),                                                     6.57(1H, d, J=9Hz), 8.04(1H, d,                                               J=9Hz)                              25    H                                                                                  ##STR15## Palely brown oily substance (75.3%) --                                               (neat) 3376, 2976, 2928, 2856, 1614, 1446,                                    1292, 1238, 1186,  1136, 1082,                                                              1.35-2.23(10H, m), 2.54-2.96                                                  (2H, m), 3.23-3.57(2H, m),                                                    3.65-4.06(4H, m), 4.06-4.43(1H,                                               m), 6.58(1H, d, J=9Hz),                                                       8.04(1H, d, J=9Hz)                  26    3-CH.sub.3                                                                        H          Colorless                                                                            (neat) 3400, 2911, 2842, 1448,                                                              1.50-1.97(6H, m), 2.20(3H, s),                           powder 1340, 1289, 1203, 1141, 1043,                                                               2.62-2.87(2H, d, J=11Hz),                                (88.7%)              3.21-3.48(2H, d, J=11Hz),                                --                   6.80(1H, s), 7.97(1H, s)            27    3-CH.sub.3                                                                        OCH.sub.3  Palely brown                                                                         (KBr) 2932, 2848, 1479, 1460,                                                               1.42-2.06(6H, m), 2.16(3H, s),                           powder 1404, 1344, 1296, 1250, 1198,                                                               2.65-2.95(2H, m), 3.20-3.46(2H,                                               m),                                                      (100%) 1006,         3.68(3H, s), 7.95(1H, s)                                 108-109° C.                                       28    3-CH.sub.3                                                                        SCH.sub.2 CH.sub.2 CH.sub.3                                                              Colorless                                                                            (KBr) 2962, 2920, 2848, 1464,                                                               0.86-1.12(3H, t, J=7Hz),                                                      1.30-2.02(8H,                                            amorphous                                                                            1446, 1290, 1230, 1140, 651,                                                                m), 1.40(3H, s), 1.48-1.73(2H,                                                t, J=7Hz),                                               powder               3.15-3.47(4H, m), 8.00(1H, s)                            (96.8%)                                                                       --                                                       __________________________________________________________________________

REFERENCE EXAMPLE 29 9-Acetoxy-2,3-cycloheptenopyridine

20 ml of acetic anhydride is added 4.9 g (30 mmol) of2,3-cycloheptenopyridine-N-oxide, and the mixture is refluxed at 90° C.for 15 hours. After cooling, excessive acetic anhydride is distilledaway under reduced pressure, and the resulting residue is extracted withethyl acetate. The ethyl acetate layer is washed successively with asaturated aqueous sodium hydrogen carbonate solution and saturatedsaline and dried over anhydrous magnesium sulfate, and the solvent isdistilled away under reduced pressure. The resulting residue is purifiedby silica gel column chromatography (ethyl acetate-n-hexane 1:3) toobtain 5.2 g (84.5%) of 9-acetoxy-2,3-cycloheptenopyridine as ayellowish oily substance.

IRν max(neat): 3050, 2932, 2856, 1736, 1454, 1438, 1368, 1234, 1040cm⁻¹.

NMR(CDCl₃)δ: 1.50-2.30(6H,m), 2.16(3H,m), 2.63-3.13(2H,m), 5.80-6.05(1H,m), 6.90-7.47(2H,m), 8.31 (1H,d,J=5 Hz).

The compounds of the following Reference examples 30 to 32 are obtainedin the same manner as above.

REFERENCE EXAMPLE 30 9-Acetoxy-4-methoxy-2,3-cycloheptenopyridine

Yellowish oily substance

Yield: 76.5%

IRν max(neat): 2932, 2856, 1736, 1580, 1476, 1372, 1288, 1236, 1046, 966818, 754 cm⁻¹.

NMR(CDCl₃)δ: 1.07-2.40(6H,m), 2.18(3H,m), 2.42-3.38(2H,m), 3.83(3H,s),5.92(1H,bs), 6.67(1H,d,J=6 Hz), 8.24(1H,d,J=6 Hz).

REFERENCE EXAMPLE 31 9-Acetoxy-4-chloro-2,3-cycloheptenopyridine

Colorless oily substance

Yield: 53.2%

IRν max(neat): 3045, 2936, 1742, 1558, 1452, 1370, 1234, 1054, 1026, 813cm⁻¹.

NMR(CDCl₃)δ: 1.20-2.35(6H,m), 2.23(3H,s), 2.58-3.63(2H,m), 5.88-6.14(1H,m), 7.26(1H,d,J=5 Hz), 8.24 (1H,d,J=5 Hz).

REFERENCE EXAMPLE 32 9-Acetoxy-4-nitro-2,3-cycloheptenopyridine

Yellowish oily substance

Yield: 7.06%

IRν max(neat): 3080, 2936, 2864, 1738, 1536, 1370, 1232, 1056, 842 cm⁻¹.

NMR(CDCl₃)δ: 1.38-2.26(6H,m), 2.18(3H,s), 2.40-3.32(2H,m), 5.84-6.13(1H,m), 7.30(1H,d,J=5 Hz), 8.48(1H,d,J=5 Hz).

REFERENCE EXAMPLE 334-Ethoxy-9-hydroxy-3-methyl-2,3-cycloheptenopyridine

7.6 ml of Acetic anhydride is added to 1.12 g (5.00 mmol) of4-ethoxy-3-methyl-2,3-cycloheptenopyridine-N-oxide, and the mixture isstirred at 90° C. for 1 hour and 40 minutes. After cooling, the reactionmixture is poured into ice water and neutralized with a 20% aqueoussodium hydroxide solution, and the mixture is extracted with chloroform.The chloroform layer is washed successively with water and saturatedsaline and dried over anhydrous magnesium sulfate, and the solvent isdistilled away under reduced pressure. The resulting residue isdissolved in 24 ml of methanol, 14 ml of a 10% aqueous sodium hydroxidesolution is added under ice cooling, and the mixture is stirred at roomtemperature for 1 hour and 46 minutes. The reaction mixture is pouredinto ice water and extracted with methylene chloride. The methylenechloride layer is washed successively with water and saturated salineand dried over anhydrous magnesium sulfate, and the solvent is distilledaway under reduced pressure. The resulting residue is purified by silicagel column chromatography (chloroformmethanol 40:1) to obtain 1.02 g(91.9%) of 4-ethoxy-9-hydroxy-3-methyl-2,3-cycloheptenopyridine as palebrown oily sustance.

IRν max(neat): 3364, 2974, 2926, 2854, 1590, 1569, 1443, 1425, 1395,1290, 1263, 1230, 1209, 1098, 1047 918, 753 cm⁻¹.

NMR(CDCl₃)δ: 1.00-2.53(7H,m), 1.43(3H,t,J=7 Hz), 2.21(3H,s), 3.10-3.46(1H,m), 3.84(2H,q,J=7 Hz), 4.67 (1H,d,J=10 Hz), 5.88(1H,bs), 8.10(1H,s).

REFERENCE EXAMPLE 34 9-Hydroxy-4-methoxy-2,3-cycloheptenopyridine

910 mg (3.87 mmol) of 9-acetoxy-4-methoxy-2,3-cycloheptenopyridine isdissolved in methanol, a 10% aqueous sodium hydroxide solution is added,and after stirring at room temperature for 1 hour, the mixture isrefluxed at 80° C. for 10 minutes. After cooling, the methanol isdistilled away under reduced pressure, and the resulting residue isextracted with methylene chloride. The methylene chloride layer iswashed with staturated saline and dried over anhydrous magnesiumsulfate, and the solvent is distilled away under reduced pressure. Theresulting solid residue is recrystallized from ether-n-hexane to obtain550 mg (73.5%) of 9-hydroxy-4-methoxy-2,3-cycloheptenopyridine asyellowish prismatic crystals having a melting point of 119° to 120° C.

IRν max(neat): 3312, 2984, 2982, 2852, 1590, 1478, 1450, 1398, 1284,1260, 1050, 866, 824, 526 cm⁻¹.

NMR(CDCl₃)δ:0.80-2.34(7H,m), 3.22-3.56 (1H,m), 3.84(3H,s),4.72(1H,d,J=11 Hz), 6.69(1H,d,J=6 Hz), 8.23 (1H,d,J=6 Hz).

The compounds of the following Reference examples 35 and 36 are obtainedin the same manner as above.

REFERENCE EXAMPLE 35 9-Hydroxy-2,3-cycloheptenopyridine

Faintly yellow oily substance

Yield: 64.9%

IRν max(neat): 3372, 2982, 2852, 1584, 1454, 1440, 1406, 1062, 796, 772cm⁻¹.

NMR(CDCl₃)δ: 0.85-3.02(7H,m), 4.48-4.95 (1H,m), 5.88(1H,bs), 6.93-7.57(2H,m), 8.32(1H,d,J=5 Hz).

REFERENCE EXAMPLE 36 4-Chloro-9-hydroxy-2,3-cycloheptenopyridine

Colorless crystalline powder

Yield: 97.6%

IRν max(KBr): 3400, 2924, 2852, 1564, 1454, 1422, 1380, 1064, 840, 778cm⁻¹.

NMR(CDCl₃)δ: 0.80-2.70(7H,m), 3.47(1H,dd,J =11 Hz,J=6 Hz),4.80(1H,d,J=11 Hz), 5.75(1H,bs), 7.18(1H,d,J=5 Hz), 8.17(1H,d,J=5 Hz).

REFERENCE EXAMPLE 37 9-Chloro-4-ethoxy-3-methyl-2,3-cycloheptenopyridine

In a stream of argon, 1.02 g (4.59 mmol) of4-ethoxy-3-methyl-9-hydroxy-2,3-cycloheptenopyridine is dissolved in 6.5ml of chloroform, 1.66 ml (23.0 mmol) of thionyl chloride is addeddropwise with stirring at -12° C., and after stirring at the sametemperature for 30 minutes, the mixture is stirred at room temperaturefor 16 hours. The reaction mixture is poured in ice water, neutralizedwith a saturated aqueous sodium hydrogen carbonate and extracted withchloroform. The chloroform layer is washed successively with water andsaturated saline and dried over anhydrous magnesium sulfate, and thesolvent is distilled away under reduced pressure to obtain crude9-chloro-4-ethoxy-3-methyl-2,3-cycloheptenopyridine as a pale brown oilysubstance.

IRν max(neat): 2976, 2928, 2860, 1564, 1460, 1384, 1336, 1286, 1266,1228, 1210, 1110, 1082, 1054, 1044, 1026, 958, 752, 736 cm⁻¹.

NMR(CDCl₃)δ: 1.20-2,56(6H,m), 1.41(3H,t,J=7 Hz), 2.21(3H,s), 2.60-3.36(2H,m), 3.81(2H,q,J=7 Hz), 5.41 (1H,d,J=5 Hz), 8.06(1H,s).

REFERENCE 38 9-Bromo-2,3-cycloheptenopyridine

1.13 g (8.16 mmol) of 9-hydroxy-2,3-cycloheptenopyridine is dissolved in10 ml of dry benzene, 0.28 ml of phosphorus tribromide is added dropwiseunder ice cooling and stirring, and the mixture is stirred overnight atroom temperature. After the reaction, ice water is added for cooling,and the mixture is neutralized with 1N sodium hydroxide and extractedwith methylene chloride. The methyhlene chloride layer is washed withsaturated saline and dried over anhydrous magnesium sulfate, and thesolvent is distilled away under reduced pressure. The resulting residueis prified by silica gel column chromatography (chloroform-methanol200:1) to obtain 391 mg (21.3%) of 9-bromo-2,3-cycloheptenopyridine asyellowish oily substance.

IRν max(neat): 3045, 2928, 2856, 1754, 1452, 1440, 1186, 964, 792, 776698, 682 cm⁻¹.

NMR(CDCl₃)δ: 1.02-3.50(8H,m), 5.58(1H,d,J= 5 Hz), 6.94-7.67(2H,m), 8.28(1H,d,J=5 Hz).

The compounds of Table-3 can be halogenated in the same manner as in theabove Reference examples 33 to 37.

EXAMPLE 1 9-(5-Methoxybenzimidazole-1-yl)thio-2,3-cycloheptnopyridine

303 mg (1.68 mmol) of 2-mercapto-5-methoxybenzimidazole is dissolved inan aqueous sodium hydroxide solution (wherein 80 mg of sodium hydroxideis dissolved in 1.4 ml of water) and 10 ml of methanol, 379 mg (1.68mmol) of 9-bromo-2,3-cycloheptenopyridine is added thereto with stirringat room temperature, and the mixture is refluxed for 1.5 hours. Aftercooling, the methanol is distilled away under reduced pressure, and theresidue is extracted with methylene chloride. The methylene chloridelayer is washed with saturated saline and dried over anhydrous magnesiumsulfate, and the solvent is distilled away under reduced pressure. Theresulting oily residue is purified by silica gel column chromatography(chloroform) and recrystallized from chloroform-n-hexane to obtain 355mg (64.9%) of9-(5-methoxybenzimidazole-2-yl)thio-2,3-cycloheptenopyridine ascolorless granular crystals having a melting point of 157° to 158° C.

IRν max(KBr): 2924, 1625, 1452, 1434, 1396, 1158 cm⁻¹.

NMR(CDCl₃)δ: 1.34-2.45(6H,m), 2.60-3.34 (2H,m), 5.08(1H,d,J=6 Hz),6.63-7.56(5H,m), 8.35(1H,d,J=5 Hz).

The compound of the following Example 2 is obtained in the same manneras above.

EXAMPLE 2 9-(Benzimidazole-2-yl)thio-2,3-cycloheptenopyridine

Colorless minute needle crystals

Melting point: 281° to 282° C.

Yield 63.4%

IRν max(KBr): 2924, 2852, 2788, 2696, 2632, 1454, 1438, 1398, 1348,1270, 746 cm⁻¹.

NMR(CDCl₃ -DMSO-D₆)δ: 1.53-2.46(6H,m), 3.35-3.67(2H,m),5.29-5.65(1H,br), 6.98-7.77(6H,m), 8.30(1H,d,J=5 Hz).

EXAMPLE 3 9-(5-nitrobenzimidazole-2-yl)thio-2,3-cycloheptenopyridine

327 mg (2 mmol) of 9-hydroxy-2,3-cycloheptenopyridine is dissolved in 3ml of chloroform from which ethanol is removed, 0.73 ml (10 mmol) ofthionyl chloride is added dropwise with cooling at -15° C., and themixture is stirred overnight at room temperature. After the reaction,the solvent is distilled away under reduced pressure, the residue isdissolved in methylene chloride, the solution is washed with saturatedsodium hydrogen carbonate, and the solvent is distilled away to obtaincrude 9-chloro-2,3-cycloheptenopyridine.

The crude 9-chloro-2,3-cycloheptenopyridine is dissolved in 5 ml ofethanol, the solution is added to ethanol (10 ml)--an aqueous sodiumhydroxide solution (wherein 120 mg of sodium hydroxide is dissolved in 2ml of water), containing 303 mg (1.68 mmol) of2-mercapto-5-nitrobenzimidazole, and the resulting mixture is refluxedfor 21 hours. After the reaction, the ethanol is distilled away underreduced pressure, and the resulting residue is extracted withchloroform. The chloroform layer is washed with saturated saline anddried over anhydrous magnesium sulfate, and the solvent is distilledaway under reduced pressure. The resulting oily residue is purified bysilica gel column chromatography (chloroform) and recrystallized fromethyl acetate-n-hexane to obtain 359 mg (52.7%) of9-(5-nitrobenzimdazole-2-yl)thio-2,3-cycloheptenopyridine as colorlessgranular crystals having a melting point of 222° to 223° C.

IRν max(KBr): 3072, 2928, 2852, 1514, 1452, 1432, 1332, 1276, 1066, 736cm⁻¹.

NMR(CDCl₃)δ: 1.54-3.34(8H,m), 5.17(1H,bs), 7.02-7.68(3H,m), 7.92-8.48(3H,m).

The compounds of the following Examples 4 to 7 are obtained in the samemanner as above.

EXAMPLE 4 9-(5-Chlorobenzimidazole-2yl)thio-2,3-cycloheptenopyridine

Yellowish candy-like substance

Yield: 78.8%

IRν max(neat): 3056, 2932, 2856, 1452, 1432, 1406, 1332, 1266, 1060, 992754 cm⁻¹.

NMR(CDCl₃)δ: 1.42-3.43(8H,m), 5.12(1H,bs), 6.94-8.85(5H,m),8.35(1H,d,J=5 Hz).

EXAMPLE 5 9-(5-Fluorobenzimidazole-2-yl)thio-2,3-cycloheptenopyridine

Colorless powder

Melting point: 202° to 203° C.

Yield: 53.6%

IRν max(KBr): 3036, 2924, 2848, 1482, 1436, 1396, 1345, 1262, 1216, 1142988, 960, 836, 802 cm⁻¹.

NMR(CDCl₃)δ: 1.30-2.53(6H,m), 2.55-3.43 (2H,m), 4.95-5.33(1H,m),6.66-7.68(5H,m), 8.32(1H,d,J=3 Hz).

EXAMPLE 6 9-(5-Methylbenzimidazole-2-yl)thio-2,3-cycloheptenopyridine

Pale yellow powder

Melting point: 207° to 208.5° C.

Yield: 44.9%

IRν max(KBr): 2924, 2848, 2784, 2616, 1434, 1390, 1276, 800 cm⁻¹.

NMR(CDCl₃)δ: 1.40-2.43(6H,m), 2.41(3H,s), 2.60-3.40(2H,m), 4.97-5.23(1H,m), 6.76-7.62(5H,m), 8.35 (1H,d,J=4 Hz).

EXAMPLE 79-(5-Trifluoromethylbenzimidazole-2-yl)thio-2,3-cycloheptenopyridine

Pale yellow amorphous powder

Yield: 53.1%

IRν max(KBr): 2932, 1452, 1432, 1328, 1280, 1246, 1160, 1116, 1050, 756cm⁻¹.

NMR(CDCl₃)δ: 1.43-2.50(6H,m), 2.56-3.23 (2H,m), 5.23(1H,bs), 6.96-7.93(5H,m), 8.17-8.53(1H,m).

EXAMPLE 89-(5-Methoxybenzimidazole-2-yl)thio-4-methoxy-2,3-cycloheptenopyridine

700 mg (3.62 mmol) of 9-hydroxy-4-methoxy-2,3-cycloheptenopyridine isdissolved in 6 ml of chloroform from which ethanol is removed, 1.3 ml(17.9 mmol) of thionyl chloride is added dropwise under cooling at -15°C., and the mixture is stirred overnight at room temperature. After thereaction, the solvent is distilled away under reduced pressure, theresidue is dissolved in methylene chloride, the resulting solution iswashed with saturated sodium hydrogen carbonate, and the solvent isdistilled away to obtain crude9-chloro-4-methoxy-2,3-cycloheptenopyridine.

The crude 9-chloro-4-methoxy-2,3-cycloheptenopyridine is dissolved in 5ml of ethanol, the solution is added to previously prepared ethanol (2ml)--an aqueous sodium hydroxide solution (wherein 290 mg of sodiumhydroxide is dissolved in 4.5 ml of water), containing 783 mg (4.34mmol) of 2-mercapto-5-methoxybenzimidazole, and the resulting mixture isrefluxed for 4.5 hours. After the reation, the ethanol is distilled awayunder reduced pressure, and the resulting residue is extracted withmethylene chloride. The methylene chloride layer is washed withsaturated saline and dried over magnesium sulfate, and the solvent isdistilled away under reduced pressure. The resulting solid residue ispurified by alumina column chromatography (ethyl acetate-n-hexane 1:3)to obtain 940 mg (73.0%) of9-(5-methoxylenzimidazole-2-yl)thio-4-methoxy-2.3-cycloheptenopyridineas colorless amorphous powder.

IRν max(KBr): 2924, 2840, 1578, 1432, 1288, 1152, 814 cm⁻¹.

NMR(CDCl₃)δ: 1.22-2.39(6H,m), 2.74-3.36 (2H,m), 3.79, 3.82(each 3H,s),5.06(1H,t,J=4 Hz), 6.62-7.60 (3H,m), 6.70(1H,d,J=6 Hz), 8.25 (1H,d,J=6Hz).

The compounds of the following Examples 9 to 11 are obtained in the samemanner as above.

EXAMPLE 9 9-(Benzimidazole-2-yl)thio-4-methoxy-2,3-cycloheptenopyridine

Colorless powder

Melting point: 176° to 179° C.

Yield: 69.8%

IRν max(KBr): 3044, 2920, 1578, 1436, 1406, 1156, 810, 752 cm⁻¹.

NMR(CDCl₃)δ: 1.14(6H,m), 2.45-3.47(2H,m), 3.82(3H,s), 5.10(1H,t,J=4 Hz),6.68(1H,d,J=6 Hz), 6.97-7.30 (2H,m), 7.30-7.63(2H,m), 8.24 (1H,d,J=6Hz).

EXAMPLE 109-(5-Flurobenzimidazole-2-yl)thio-4-methoxy-2,3-cycloheptenopyridine

Yellowish powder

Melting point: 93° to 95° C.

Yield: 74.8%

IRν max(KBr): 3045, 2976, 2928, 1628, 1580, 1438, 1290, 1134, 1052, 838cm⁻¹.

NMR(CDCl₃)δ: 1.15-2.43(6H,m), 2.53-3.50 (2H,m), 3.83(3H,s),5.08(1H,bs),6.54-7.52(3H,m), 6.72(1H,d,J=6 Hz), 8.25(1H,d,J=6 Hz).

EXAMPLE 119-(5-Methyoxybenzimidazole-2-yl)thio-4-chloro-2,3-cycloheptenopyridine

Colorless powder

Melting point: 113° to 116° C.

Yield: 63.4%

IRν max(KBr): 2928, 1625, 1560, 1490, 1456, 1432, 1404, 1346, 1200,1154, 834 cm⁻¹.

NMR(CDCl₃)δ: 1.40-2.52(6H,m), 3.07-3.38 (2H,m),3.80(3H,s), 5.06-5.33(1H,m), 6.63-7.60(4H,m), 8.20 (1H,d,J=5 Hz).

EXAMPLE 129-(Benzimidazole-2-yl)thio-4-(2-hydroxyethoxy)-2,3-cycloheptenopyridine

In a stream of argon, 1.48 g (3.32 mmol) of9-(benzimidazole-2-yl)thio-4-(2-benzyloxyethoxy)-2,3-cycloheptenopyridineis suspended in 7.5 ml of methylene chloride 7.5 ml of dimethyl sulfideis added and dissolved under ice cooling and stirring, 3.75 ml (30.5mmol) of a trifluoroborane-ether complex is added dropwise, and theresulting mixture is stirred for 30 minutes under ice cooling andfurther for 12 hours at room temperature. After completion of thereaction, the reaction mixture is poured into ice water, and theresulting mixture is made weakly alkaline with potassium carbonate andextracted with chloroform. The chlorform layer is washed successivelywith water and saturated saline and dried over anhydrous magnesiumsulfate, and the solvent is distilled away under reduced pressure. Theresulting residue is separated and purified by silica gel columnchromatography (chloroform-methanol 30:1) to obtain 1.18 g (99.8%) of9-(benzimidazole-2-yl)thio-4-(2-hydroxyethoxy)-2,3-cycloheptenopyridineas colorless amorphous powder.

IRν max(KBr): 3154, 3064, 2926, 2854, 1581, 1470, 1437, 1407, 1350,1290, 1269, 1230, 1092, 1053, 903, 813, 741 cm⁻¹.

NMR(CDCl₃)δ: 1.20-3.40((8H,m), 3.95-4.35 (4H,m), 4.96-5.20(1H,m), 6.70(1H,d,J=6 Hz), 6.99-7.55(4H,m), 8.22(1H,d,J=6 Hz).

EXAMPLE 134-(2-Acetoxyethoxy)-9-(benzimidazole-2-yl)thio-2,3-cycloheptenopyridine

In a stream of argon, 573 mg (1.44 mmol) of9-(benzimidazole-2-yl)thio-4-(2-hydroxyethoxy)-2,3-cycloheptenopyridineis dissolved in 6 ml of methylene chloride, 0.46 ml (5.76 mmol) ofpyridine is added dropwise with stirring at room temperature andsuccessively 0.27 ml (2.88 mmol) of acetic anhydride is added dropwise,and the resulting mixture is stirred at room temperature for 14 hoursand 30 minutes. After cooling, the reaction mixture is poured into icewater, followed by extraction with chloroform. The chloroform layer iswashed successively with water and saturated saline and dried overanhydrous magnesium sulfate, and the solvent is distilled away underreduced pressure. The resulting residue is purified by silica gel columnchromatography (chloroform-methanol 30:1). The resulting oily substanceis dissolved in methylene chloride, 7.28 g of silica gel is added, themixture is stirred at room temperature for 1 hour, the silica gel isfiltered off, and then the methylene chloride is distilled away underreduced pressure to obtain 520 mg (90.9%) of9-(benzimidazole-2-yl)thio-4-(2-acetoxyethoxy)-2,3-cycloheptenopyridineas a colorless oily substance.

IRν max(Neat): 2928, 1740, 1580, 1470, 1452, 1438, 1406, 1290, 1268,1228, 1094, 1058, 908, 736, 648, 604 cm⁻¹.

NMR(CDCl₃)δ: 1.18-2.42(6H,m), 2.70(3H,s), 2.56-3.41(2H,m), 4.06-4.30(2H,m), 4.30-4.54(2H,m), 4.99-5.22(1H,m), 6.69(1H,d,J=6 Hz),6.96-7.26(2H,m), 7.30-7.62 (2H,m), 8.24(1H,d,J=6 Hz).

EXAMPLE 144-Ethoxy-9-(5-methoxybenzimidazole-2-yl)thio-3-methyl-2,3-cycloheptenopyridine

Crude 9-chloro-4-ethoxy-3-methyl-2,3-cycloheptenopyridine (4.95 mmol) isdissolved in 16 ml of ethanol, 892 mg (4.95 mmol) of5-methoxy-2-mercaptobenzimidazole and 16 ml of a 20% aqueous sodiumhydroxide solution are added, and the mixture is refluxed with heatingfor 20 hours. After cooling, the solvent is distilled away under reducedpressure and the residue is extracted with chloroform. The chloroformlayer is washed successively with a saturated aqueous sodium hydrogencarbonate solution, water and saturated saline and dried over anhydrousmagnesium sulfate, and the solvent is distilled away under reducedpressure. The resulting residue is subjected to active alumina columnchromatography (ethy acetate:hexane 2:3→ethyl acetate→ethylacetate:methanol 100:1) to obtain 799 mg (42.1%) of4-ethoxy-9-(5-metoxybenzimidazole-2-yl)thio-3-methyl-2,3-cycloheptenopyridineas colorless amorphous powder.

IRν max(KBr): 2976, 2924, 2852, 1626, 1450, 1398, 1344, 1288, 1268,1228, 1200, 1154, 1052, 1026, 960, 838, 802 cm⁻¹.

NMR(CDCl₃)δ: 1.10-2.40(6H,m), 1.43(3H,t,J=7 Hz), 2.23(3H,s), 2.65-3.33(2H,m), 3.65-4.03(2H,m), 3.81 (3H,s), 4.93-5.16(1H,m), 6.65-7.65(3H,m),8.14(1H,s).

EXAMPLE 159-[1-(Benzyloxycarbonyl)benzimidazole-2-yl]thio-4-methoxy-2,3-cycloheptenopyridine

In a stream of argon, 520 mg (1.60 mmol) of9-(benzimidazole-2-yl)thio-4-methoxy-2,3-cycloheptenopyridine isdissolved in 10 ml of THF, 215 mg (1.90 mmol) of potassium t-butoxide(t-Buok) dissolved in 8 ml of THF is added dropwise under ice coolingand stirring, and the mixture is stirred at room temperature for 20minutes. Then, 607 mg (3.20 mmol) of carbobenzoxy chloride dissolved in2 ml of THF is added dropwise, and the mixture is stirred at roomtemperature for 30 minutes. After completion of the reaction, asaturated aqueous ammonium chloride solution is added to the reactionmixture, followed by extraction with methylene chloride. The methylenechloride layer is washed successively with water and saturated salineand dried over anhydrous magnesium sulfate, and the solvent is distilledaway under reduced pressure. The resulting residue is crystallized fromchloroform-hexane to obtain 657 mg (89.5%) of9-[1-(benzyloxycarbonyl)benzimidazole-2-yl]thio-4-methoxy-2,3-cycloheptenopyridineas colorless powder having a melting point of 181° to 184° C.

IRν max(KBr): 3430, 2910, 1736, 1576, 1466, 1450, 1392, 1332, 1294,1280, 1254, 1194, 1078 cm⁻¹.

NMR(CDCl₃)δ:1.36-2.94(7H,m), 3.06-3.33 (1H,m), 3.82(3H,s), 5.50(2H,s),5.66(1H,d,J=9.0 Hz), 6.65(1H,d,J =7.5 Hz), 6.97-7.86(9H,m), 8.23(1H,d,J=7.5 Hz).

EXAMPLE 169-[1-(hydroxymethyl)benzimidazole-2-yl]thio-4-methoxy-2,3-cycloheptenopyridine

958 mg (2.95 mmol) of9-(benzimidazole-2-yl)thio-4-methoxy-2,3-cycloheptenopyridine isdissolved in 16 ml of acetonitrile and 16 ml of methylene chloride, andunder stirring 0.36 ml (4.42 mmol) of 37% formaldehyde dissolved in 1 mlof acetonitrile is added dropwise. The mixture is then stirred for 30minutes and further at 70° C. for 45 minutes. The reaction mixture ispoured into ice water, followed by extraction with methylene chloride.The methylene chloride layer is washed successively with water andsaturated saline and dried over anhydrous magnesium sulfate, and thesolvent is distilled away under reduced pressure. The resulting residueis crystallized from methylene chloride-hexane to obtain 676 mg (64.6%)of9-[1-(hydroxymethyl)benzimidazole-2-yl]thio-4-methoxy-2,3-cycloheptenopyridineas colorless powder having a melting point of 136° to 138° C. The motherliquor is evaporated under reduced pressure, and the resulting residueis crystallized from methylene chloride-ether-hexane to obtain 246 mg(23.5%) of the above compound (total yield 88.1%).

IRν max(KBr): 3132, 2968, 2936, 1578, 1474, 1466, 1428, 1366, 1330,1304, 1288, 1250, 1136, 1102, 1082 cm⁻¹.

NMR(CDCl₃)δ: 1.33-3.20(8H,m), 3.80(3H,s), 4.81-5.16(1H,m), 5.73(2H,q,J=9 Hz), 6.60(1H,d,J=7.5 Hz), 7.03-7.86(4H,m), 8.00(1H,d,J=7.5 Hz).

EXAMPLE 179-[1-(t-Butoxycarbonylmethoxymethyl)benzimidazole-2-yl]thio-4-methoxy-2,3-cycloheptenopyridine

In a stream of argon, 48 mg (1.20 mmol) of 60% sodium hydride issuspended in 5 ml of THF, and under ice cooling and stirring, 355 mg(1.00 mmol) of9-[1-(hydroxymethyl)benzimidazole-2-yl]thio-4-methoxy-2,3-cycloheptenopyridinedissolved in 5 ml of THF is dropwise added by portions. The resultingmixture is stirred at room temperature for 45 minutes. Then, under icecooling and stirring, t-butoxycarbonyl bromide dissolved in 2 ml of THFis added dropwise, and the mixture is stirred at room temperature for 16hours. After the reaction, the reaction mixture is poured into asaturated aqueous ammonium chloride solution, followed by extractionwith methylene chloride. The methylene chloride layer is washedsuccessively with water and saturated saline and dried over anhydrousmagnesium sulfate, and the solvent is distilled away under reducedpressure to obtain 427 mg (91.2%)9-[1-(t-butoxycarbonylmethoxymethyl)benzimidazole-2-yl]thio-4-methoxy-2,3-cycloheptenopyridine

IRν max(KBr): 2976, 2928, 1744, 1626, 1578, 1474, 1444, 1368, 1334,1314, 1282, 1232, 1156, 1114, 1092 cm⁻¹.

NMR(CDCl₃)δ: 1.40(9H,s), 1.60-2.80(7H,m), 3.16-3.46(1H,m), 3.83(3H,s)4.83(2H,s), 5.50-5.75(1H,m), 5.70(2H,s), 6.67(1H,d,J=7.5 Hz),7.04-7.80(4H,m), 8.10-8.28 (1H,d,J=7.5 Hz).

EXAMPLE 18 9-[pyrido[2,3-d]imidazole-2-yl]thio-2,3-cycloheptenopyridine

Crude 9-chloro-2,3-cycloheptenopyridine (9.15 mmol) is dissolved in 29ml of ethanol, 1.38 g (9.15 mmol) of 2-mercaptopyrido [2,3-d] imidazoleand 29 ml of a 20% aqueous sodium hydroxide solution are added thereto,and the mixture is refluxed with heating for 20 hours. After cooling,the solvent is distilled away under reduced pressure, and the residue isextracted with chloroform. The chloroform layer is washed successivelywith a saturated aqueous sodium hydrogen carbonate solution, water andsaturated saline, and dried over anhydrous magnesium sulfate, and thesolvent is distilled away under reduced pressure. The resulting residueis subjected to activated alumina column chromatography (ethylacetate:hexane 2:3→ethyl acetate→ethyl acetate:methanol 100:1) to obtain700 mg (25.8%) of9-[pyrido[2,3-d]imidazaole-2-yl]thio-2,3-cycloheptenopyridine ascolorless amorphous powder.

IRν max(KBr): 2921, 1452, 1439, 1393, 1268, 768, 753 cm⁻¹.

NMR(CDCl₃)δ: 1.39-2.60(6H,m), 2.60-3.30 (2H,m), 5.13-5.33(1H,m),6.97-7.30(2H,m), 7.31-7.60(1H,m), 7.56-7.92(1H,m), 8.15-8.50 (2H,m).

The compounds in Table-4 are obtained in the same manner as in Examples1 to 18.

    TABLE 4      ##STR16##       Example      Melting point   No. R R.sup.1 R.sup.2 R.sup.3 A (yield)     IR νcm.sup.-1 NMR(CDCl.sub.3)δ       19 H OEt H H CH Colorless amor- (KBr) 3432, 2976, 2924, 1464, 1.43(3H,     t, J=7.5Hz), 1.66-3.32(8H, m),       phous powder 1438, 1290, 1268,     1232, 1088, 4.03(2H, q, J=7.5Hz), 5.19(1H, t, J=6Hz),       (74.2%)     6.65(1H, d, J=9Hz), 6.96-7.66(4H, m),       --  8.22(1H, d, J=9Hz) 20 H     O-n-Bu H H CH Colorless powder (KBr) 3429, 3064, 2928, 1580, 0.96(3H, t,     J=7.5Hz), 1.12-2.43(10H, m),       (55.8%) 1460, 1438, 1288, 1268, 1088,     2.60-3.31(2H, m), 3.96(2H, t, J=7.5Hz),       65-70° C.  5.18(1H,     t, J=6Hz), 6.66(1H, d, J=7.5Hz),         6.86-8.64(4H, m), 8.22(1H, d,     J=7.5Hz)      21 H     ##STR17##      H H CH Palely yellowneedle crystal(55.4%)222-223° C. (KBr) 3430,     2928, 1576, 1504,1460, 1438, 1398, 1348, 1332,1270, 1250, 1204, 1162,     1.36-3.55(8H, m), 2.33(3H, s), 5.03-5.30(1H, m), 6.50(1H, d, J=7.5Hz),     6.84(2H, d,J=7.5Hz), 6.96-7.66(6H, m), 8.13(1H, d,J=7.5Hz)  22 H      ##STR18##      H H CH Colorless powder(46.4%)159-160° C. (KBr) 3460, 3080,     3032, 2960,2924, 1582, 1462, 1450, 1430,1404, 1350, 1272, 1042, 1008,     0.13-0.76(4H, m), 1.10-1.64(1H, m),1.66-3.46(8H, m), 3.83(1H, d,     J=7.5Hz),5.10(1H, t, J=6Hz), 6.65(1H, d, J=7.5Hz),6.97-7.64(4H, m),     8.22(1H, d, J=7.5Hz)      23 H     ##STR19##      H H CH Colorless amor-phous powder(82.9%)-- (KBr) 2972, 2928, 2860,     1578,1438, 1406, 1346, 1290, 1268,1230, 1082, 1050, 1.36-2.53(10H, m),     2.64-3.36(1H, m),3.73-4.36(5H, m), 5.08(1H, t, J=6Hz),6.70(1H, d,     J=7.5Hz), 6.94-7.76(4H, m),8.23(1H, d, J=7.5Hz)  24 H OCH.sub.3 H     CH.sub.2 OCOCH.sub.3 CH Colorless powder (KBr) 2924, 1750, 1578, 1472,     1.63-2.85(7H, m), 2.03(3H, s), 3.07-3.46       (61.1%) 1440, 1352, 1280,     1260, 1212, (1H, m), 3.83(3H, s), 5.64(1H, d, J=10.5       160-162.degree     . C. 1052, 1018, Hz), 6.15(2H, d, d, J=30Hz, J=30Hz), 6.67         (1H,     d, J=7.5Hz), 7.06-7.76(4H, m), 8.23         (1H, d, J=7.5Hz) 25 H     OCH.sub.3 H CH.sub.2 OCH.sub.3 CH Colorless amor- (KBr) 2928, 2852,     1578, 1432, 1.56-2.86(7H, m), 3.10-3.46(1H, m), 3.29       phous powder     1334, 1283, 1268, 1112, 1092, (3H, s), 3.83(3H, s), 5.52(2H, s), 5.68,         (71.0%) 1056, (1H, d, J=9Hz), 6.66(1H, d, J=7.5Hz),       --     7.06-7.78(4H, m), 8.22(1H, d, J=7.5Hz) 26 H OCH.sub.3 H CH.sub.2 OEt CH     Colorless candy- (neat) 2976, 2928, 2856, 1578, 1.43(3H, t, J=9Hz),     1.62-2.43(7H, m),       like substance 1474, 1434, 1394, 1264, 1092,     2.46-2.85(1H, m) 3.50(2H, q, J=9Hz),       (66.8%) 1056, 942, 3.80(3H,     s), 5.55(2H, s), 5.67(1H, d,       --  J=10.5Hz), 6.65(1H, d, J=7.5Hz),     7.06-7.75         (4H, m), 8.22(1H, d, J=7.5Hz) 27 H OCH.sub.3 H     CH.sub.2 O(CH.sub.2).sub.2 OCH.sub.3 CH Colorless candy- (neat) 2924,     2852, 1578, 1472, 1.54-2.86(8H, m), 3.14-3.84(4H, m), 3.29       like     substance 1332, 1282, 1264, 1134, 1090, (3H, s), 3.81(3H, s), 3.50-3.81(1     H, m),       (91.7%) 1056, 3.51(2H, m), 6.64(1H, d, J=7.5Hz),       --     7.05-7.73(4H, m), 8.11(1H, m) 28 H OCH.sub.3 H COO(CH.sub.2).sub.2     OCH.sub.3 CH Palely yellow (KBr) 2920, 2848, 1746, 1578, 1.62-2.94(8H,     m), 3.43(3H, s), 3.76(2H,       powder 1452, 1406, 1384, 1332, 1264, t,     J=6Hz), 3.82(3H, s), 4.62(2H, t, J=6Hz),       (90.6%) 1192, 1138, 1076,     5.53-5.83(1H, m), 6.65(1H, d, J=7.5Hz),       150-151° C.     7.04-7.98(4H, m), 8.22(1H, d, J=7.5Hz) 29 H OCH.sub.2 CF.sub.2 CF.sub.3     H H CH Colorless amor- (KBr) 2928, 1578, 1440, 1404, 1.13-2.40(6H, m),     2.70-3.38(2H, m), 4.46       phous powder 1350, 1294, 1268, 1198, 1152,     (2H, t, J=12Hz), 5.20(1H, t, J=4Hz), 6.69       (58.1%) 1100, 740 (1H,     t, J=5Hz), 7.00-7.78(4H, m), 8.33       --  (1H, d, J=5Hz) 30 H OCH.sub.2      CF.sub.2 CF.sub.2 H H H CH Colorless amor- (KBr) 3064, 2929, 2856,     1578, 1.10-2.42(6H, m), 2.73-3.35(2H, m), 4.38       phous powder 1470,     1454, 1438, 1404, 1348, (2H, m), 5.18(1H, br), 5.38, 5,98, 6.57     (51.7%) 1312, 1290, 1268, 1228, 1200, (1H, t×3, J=3Hz), 6.70(1H,     d, J=6Hz),       -- 1106, 1062, 942, 836, 810, 742, 7.00-7.75(4H, m),     8.32(1H, d, J=6Hz) 31 H OCH.sub.2      Ph H H CH Colorless amor-  1.15-2.45(6H, m), 2.63-3.40(2H, m),     phous powder  5.05(2H, s), 5.20(1H, t, J=4Hz), 6.70       (65.0%)  (1H,     d, J=5Hz), 7.10-7.95(4H, m), 7.31       --  (5H, s), 8.21(1H, d, J=5Hz)     32 H SCH.sub.2 CH.sub.2 CH.sub.3 H H CH Colorless amor-  1.08(3H, t,     J=7Hz), 1.20-3.68(12H, m),       phous powder  5.20(1H, br), 6.97(1H, d,     J=5Hz),       (42.0%)  7.00-7.95(4H, m), 8.21(1H, d, J=5Hz),       --     33 H      ##STR20##      H H CH Colorless powder(56.4%) 215-217° C. (KBr) 2960, 2924,     2852, 1580,1446, 1420, 1394, 1342, 1270,1252, 1116, 988, 904, 740,     1.08-2.47(6H, m), 2.73-3.35(6H, m),3.67-4.05(4H, m), 5.04-5.25(1H, m),     6.80(1H, d,J=6Hz), 7.00-7.76(4H, m), 8.26(1H, d, J=6Hz)  34 H OCH.sub.2     CH.sub.2 OCH.sub.3 5-F H CH Colorless powder (KBr) 2928, 2856, 1582,     1474, 1.13-2.53(6H, m), 2.63-3.30(2H, m), 3.42       (43.6%) 1432, 1404,     1346, 1286, 1260, (3H, s), 3.63-3.86(2H, m), 4.02-4.24(2H, m),     141-142° C. 1230, 1196, 1130, 1110, 1084, 4.98-5.20(1H, m),     6.72(1H, d, J=7Hz),        1056, 1036, 966, 952, 800, 6.76-7.57(3H, m),     8.22(1H, d, J=7Hz) 35 H OCH.sub.3 5,6-OCH.sub.3 H CH Colorless powder     (KBr) 2932, 1578, 1488, 1472, 1.03-2.35(6H, m), 2.63(2H, m), 3.84(3H,     s),       (38.9%) 1440, 1420, 1398, 1328, 1282, 3.88(6H, s), 4.86-5.10(1H     , m), 6.70(1H, d,       112-114.5° C. 1196, 1170, 1136, J=6Hz),     6.75-7.16(2H, m), 8.25(1H, d, J=6Hz) 36 H OCH.sub.2 CF.sub.3 H H CH     Palely yellow (KBr) 3064, 2856, 1578, 1470, 1.40-2.50(6H, m), 2.71-3.41(2     H, m),       amorphous powder 1454, 1438, 1404, 1348, 1316, 4.37(2H, q,     J=9Hz), 5.03-5.26(1H, m),       (47.6%) 1290, 1264, 1230, 1166, 1138,     6.67(1H, d, J=6Hz), 7.00-7.70(4H, m),       -- 1100, 1064, 974, 8.30(1H,     d, J=6Hz) 37 H OCH.sub.2 CHCH.sub.2 H H CH Colorless powder (KBr) 2924,     2852, 1578, 1468, 1.05-2.36(6H, m), 2.65-3.36(2H, m),       (51.6%)     1436, 1404, 1346, 1310, 1282, 4.50(2H, d, J=4Hz), 4.96-5.36(2H, m),      106-108° C. 1268, 1230, 1044, 1016, 930, 5.37(1H, d, J=9Hz),     5.66-6.23(1H, m),        816, 740, 6.63(1H, d, J=5Hz), 6.93-7.30(2H, m),             7.30-7.60(2H, m), 8.18(1H, d, J=5Hz) 38 H OCH.sub.2 CH.sub.2     OCH.sub.3 H H CH Colorless powder (KBr) 2976, 2924, 2852, 1578, 1.33-2.35     (6H, m), 2.65-3.23(2H, m), 3.39       (56.3%) 1470, 1438, 1402, 1288,     1266, (3H, s), 3.56-3.83(2H, m), 3.93-4.25(2H, m),       124-125°     C. 1234, 1196, 1128, 1088, 1056, 5.02-5.26(1H, m), 6.68(1H, d, J=6Hz),          740, 6.93-7.28(2H, m), 7.28-7.62(2H, m),         8.21(1H, d, J=6Hz)     39 H O(CH.sub.2).sub.3 OCH.sub.3 H H CH Colorless amor- (KBr) 2924,     2856, 1578, 1460, 1.13-2.40(8H, m), 2.57-3.20(2H, m), 3.30       phous     powder 1438, 1400, 1286, 1266, 1228, (3H, s), 3.51(2H, t, J=6Hz),     4.07(2H, t, J=6Hz),       (38.5%) 1116, 1088, 1050, 814, 738, 4.99-5.17(1     H, m), 6.69(1H, d, J=6Hz),       --  6.95-7.78(4H, m), 8.22(1H, d,     J=6Hz) 40 H O(CH.sub.2).sub.2 OCH.sub.2 Ph H H CH Colorless powder (KBr)     2924, 2852, 2804, 1580, 1.10-2.50(6H, m), 2.56-3.53(2H, m),     (52.5%) 1440, 1400, 1290, 1270, 1120, 3.70-3.97(2H, m), 4.00-4.36(2H,     m),       168-169° C. 750, 732, 4.59(2H, s), 4.98-5.21(1H, m),     6.70(1H, d,         J=6Hz), 6.97-7.63(9H, m), 8.24(1H, d, J=6Hz) 41 H     O(CH.sub.2).sub.2 OPh H H CH Colorless amor- (KBr) 3056, 2924, 2852,     1598, 1.50-2.50(6H, m), 2.60-3.40(2H, m)       phous powder 1578, 1496,     1470, 1436, 1402, 4.33(4H, s), 5.00-5.21(1H, m),       (50.9%) 1288,     1266, 1242, 1172, 1090, 6.66-7.81(9H, m), 8.26(1H, d, J=6Hz)       --     1056, 740, 690, 42 H O(CH.sub.2).sub.2 OCH.sub.2 Py H H CH Colorless     amor- (KBr) 2920, 2852, 1576, 1470, 1.35-2.40(6H, m), 2.55-3.41(2H, m),          phous powder 1436, 1404, 1348, 1286, 1266, 3.86-4.05(2H, m),     4.15-4.36(2H, m),       (32.8%) 1232, 1134, 1088, 1048, 760, 4.69(2H,     s), 4.96-5.21(1H, m), 6.70       -- 740, (1H, d, J=6Hz), 6.93-7.76(7H,     m),         8.23(1H, d, J=6Hz), 8.49(1H, d, J=4Hz)      43 H     ##STR21##      H H CH Colorless amor-phous powder(36.5%)-- (KBr) 2932, 1676, 1580,     1460,1438, 1290, 1268, 1232, 1092,908, 732, 648, 1.10-3.21(12H, m),     3.50(2H, t, J=7Hz), 3.70(2H, t, J=6Hz), 3.98-4.23(2H, m), 5.01-5.24(1H,     m), 6.66(1H, d, J=7Hz), 7.00-7.30(2H, m), 7.30-7.75(2H, m), 8.23(1H, d,     J=7Hz)  44 3-CH.sub.3 4-OCH.sub.2 CF.sub.2 CF.sub.2 H 5-F H CH Palely     yellow (KBr) 3064, 2932, 2856, 1490, 1.20-2.60(8H, m), 2.27(3H, s),     2.67-3.25       amorphous powder 1440, 1406, 1346, 1288, 1262, (2H, m),     4.14(2H, t, J=14Hz), 5.00-5.20       (55.8%) 1226, 1200, 1134, 1108,     1062, (1H, m), 5.35-7.50(5H, m), 8.19(1H, s)       -- 958, 836, 804, 45     3-CH.sub.3 4-OCH.sub.3 5-OCH.sub.3 H CH Yellow amorphous (KBr) 2924,     2848, 1468, 1450, 1.40-2.46(6H, m), 2.23(3H, s), 2.65-3.35       powder     1432, 1394, 1342, 1260, 1232, (2H, m), 3.69(3H, s), 3.79(3H, s),     (36.8%) 1198, 1152, 1054, 1030, 1006, 4.93-5.13(1H, m), 6.63-7.65(2H,     m), 8.14(1H, s)       -- 46 H OCH.sub.2 CH.sub.2 OCH.sub.3 5-CH.sub.3 H     CH Palely yellow (neat) 2980, 2924, 2856, 1736, 1.65-2.43(6H, m),     2.40(3H, s), 2.63-3.25       amorphous powder 1580, 1448, 1372, 1334,     1274, (2H, m), 3.46(3H, s), 3.63-3.83(2H, m),       (37.6%) 1240, 1198,     1132, 1090, 1060, 3.99-4.24(2H, m), 4.96-5.16(1H, m), 6.68       -- 806,     754, 600, (1H, d, J=7Hz), 6.91(1H, d, J=11Hz),         7.07-7.47(2H, m),     8.22(1H, d, J=7Hz) 47 3-CH.sub.3 4-OCH.sub.2 CF.sub.2 CF.sub.2 H     5-OCH.sub.3 H CH Yellow amorphous (KBr) 2928, 1452, 1400, 1344, 1.40-2.38     (6H, m), 2.26(3H, s), 2.86-3.15       powder 1270, 1226, 1198, 1154,     1100, (2H, m), 3.80(3H, s), 4.12(2H, t, J=12Hz),       (58.1%) 1062,     1026, 834, 806, 754, 5.00-5.20(1H, m), 5.10, 6.03, 6.62(1H, t×3,         --  J=4Hz), 6.75-7.35(3H, m), 8.18(1H, s) 48 H OCH.sub.2 CH.sub.2     OCH.sub.3 H COOCH.sub.2 CH.sub.2 OCH.sub.3 CH Colorless needle (KBr)     2928, 1744, 1574, 1452, 1.20-2.97(8H, m), 3.44(6H, s), 3.63-3.91     crystal 1382, 1324, 1300, 1282, 1264, (4H, m), 4.03-4.23(2H, m),     4.50-4.73(2H, m),       (79.0%) 1192, 1120, 1078, 758, 5.68(1H, d,     J=7Hz), 6.66(1H, d, J=6Hz), 7.07-       130-131° C.  7.33(2H, m),     7.46-7.70(1H, m), 7.76-7.96         (1H, m), 8.21(1H, d, J=6Hz) 49     3-CH.sub.3 OCH.sub.2 CH.sub.2 OCH.sub.3 H H CH Colorless amor- (KBr)     2920, 1440, 1401, 1269, 1.30-1.65(7H, m), 3.49(3H, s), 2.93-3.60     phous powder 1058, 748, (1H, m), 3.86(3H, s), 3.95-4.15(2H, d, J=7     (43.9%)  Hz), 4.20-4.40(2H, d, J=7Hz), 5.52-6.70       --  (1H, m),     7.70-8.43(4H, m), 8.95(1H, s) 50 3-CH.sub.3 OCH.sub.2 CH.sub.2 OCH.sub.3     5-F H CH Colorless amor- (KBr) 2920, 1438, 1401, 1340, 1.50-2.35(7H, m),     2.26(3H, s), 2.70-3.22       phous powder 1259, 1129, 1051, 959 (1H, m),     3.42(3H, s), 3.55-3.80(2H, d, J=6       (31.3%)  Hz), 3.80-4.00(2H, d,     J=6Hz), 4.97-5.20       --  (1H, m), 6.69-7.52(3H, m), 8.15(1H, s) 51     3-CH.sub.3 OCH.sub.3 5-F H CH Colorless amor- (KBr) 2926, 2854, 1470,     1437, 1.25-2.50(6H, m), 2.26(3H, s), 2.63-3.36       phous powder 1404,     1347, 1260, 1134, 750, (2H, m), 4,72(3H, s), 5.00-5.16(1H, m),     (65.1%)  6.74-7.50(3H, m), 8.15(1H, s)       -- 52 H OCH.sub.3 H     CH.sub.2 COOEt CH Colorless powder (KBr) 2976, 2924, 1736, 1578,     1.23(3H, t, J=9Hz), 1.56-2.76(7H, m),       (66.8%) 1474, 1460, 1440,     1330, 1310, 3.10-3.48(1H, m), 3.82(3H, s), 4.17(2H, q       162-163.5.deg     ree. C. 1282, 1244, 1210, 1054, 1024, J=9Hz), 4.92(2H, s), 5.62(1H, d,     J=12Hz),         6.66(1H, d, J=7.5Hz), 7.07-7.83(4H, m),     8.22(1H, d, J=7.5Hz) 53 3-CH.sub.3 OCH.sub.3 H H CH Colorless powder     (KBr) 3432, 2928, 2856, 1468, 1.30-2.42(7H, m), 2.23(3H, s), 2.73-3.15         (57.4%) 1440, 1398, 1270, (1H, m), 3.70(3H, s), 5.01-5.16(1H, m),        196-196.5° C.  6.96-7.71(4H, m), 8.15(1H, s) 54 H OCH.sub.3     5-CH.sub.3 H CH Colorless amor- (KBr) 2920, 2848, 1578, 1470, 1.39-3.40(8     H, m). 1.42(3H, s), 3.83(3H, s),       phous powder 1437, 1275, 1230,     1050, 801, 5.00-5.17(1H, t, J=5Hz), 6.63-6.77(1H, d,       (74.0%)     J=7Hz), 6.86-7.03(1H, d, J=10Hz), 7.10-7.53       94-95° C.  (2H,     m), 8.03-8.18(1H, d, J=6Hz) 55 3-CH.sub.3 SCH.sub.2 CH.sub.2 CH.sub.3 H     H CH Colorless powder (KBr) 2962, 2920, 2848, 1440, 0.87-1.13(3H, t,     J=7Hz), 1.12-2.40(8H, m),       (62.4%) 1401, 1377, 1350, 1269, 1236,     2.49(3H, s), 2.50-2.76(2H, t, J=7Hz),       182-183° C. 744,     3.00-3.79(2H, m), 5.06-5.28(1H, m), 7.00-7.27         (2H, m), 7.35-7.60(     1H, m), 8.21(1H, s), 56 H OCH.sub.2 CH.sub.2 OCH.sub.3 H H N Colorless     amor- (KBr) 2921, 1578, 1450, 1396, 1.44-3.22(8H, m), 3.41(3H, s),     3.63-3.85       phous powder 1269, 1232, 1122, 1057, (2H, m), 4.00-4.22(2     H, m), 5.08-5.25(1H, m),       (26.3%)  6.65-6.77(1H, d, J=7Hz),     6.96-7.18(1H, m),       --  7.68-8.89(1H, m), 8.10-8.38(2H, m) 57 H     OCH.sub.3 H H N Colorless amor- (KBr) 2950, 1590, 1468, 1408, 1.30-3.16(8     H, m), 3.83(3H, s), 5.09-5.28       phous powder 1293, 1065, 759, (1H,     m), 6.60-6.77(1H, m), 6.96-7.18(1H, m),       (25.8%)  7.56-7.86(1H, m),     8.08-8.37(2H, m),       -- 58 3-CH.sub.3 H H H N Colorless amor- (KBr)     2930, 1470, 1401, 1060, 1.44-3.30(8H, m), 2.28(3H, s), 5.10-5.31     phous powder 799, (1H, m), 6.92-7.35(2H, m), 7.70-7.93       (21.0%)     (1H, d, J=10Hz), 8.05-8.38(2H, s)       -- 59 3-CH.sub.3 OCH.sub.3 H H N     Colorless powder (KBr) 2930, 1590, 1470, 1070, 1.30-3.42(8H, m),     2.24(3H, s), 3.72(3H, s),       (46.1%) 810, 5.06-5.20(1H, m), 6.98-7.20(     1H, m),       --  7.69-7.86(1H, d, J=10Hz), 8.20(2H, s) 60 3-CH.sub.3     OCH.sub.2 CF.sub.2 CF.sub.2 H H H N Colorless amor- (KBr) 2925, 1456,     1397, 1272, 1.60-2.30(5H, m), 2.26(3H, s), 2.87-3.21       phous powder     1011, 957, 779, (3H, m), 3.95-4.32(3H, t, J=12Hz), 5.17-5.39     (53.5%)  (1H, m), 5.38-6.71(2H, m), 6.96-7.23(1H, m),       --  7.72-7.91     (1H, d, J=9Hz), 8.15-8.31(2H, s)

EXAMPLE 619-(5-Methoxybenzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridine

940 mg (2.64 mmol) of9-(5-methoxybenzimidazole-2-yl)thio-4-methoxy-2,3-cycloheptenopyridineis dissolved in 48 ml of dry methylene chloride, 456 mg (2.64 mmol) ofm-chloroperbenzoic acid is added portionwise with stirring at -18° C.,and the mixture is stirred for 20 minutes. After the reaction, asaturated aqueous sodium hydrogen carbonate solution is added, followedby extraction with methylene chloride. The methylene chloride layer iswashed with saturated saline and dried over anhydrous magnesium sulfate,and the solvent is distilled away under reduced pressure. The resultingcrystalline residue is recrystallized from chloroform-ether to obtain564 mg (57.4%) of9-(5-methoxybenzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridineas yellowish powder having a melting point of 145° to 148° C.

IRν max(KBr): 2936, 1580, 1476, 1436, 1286, 1008 cm⁻¹.

NMR(CDCl₃)δ: 0.98-2.43(7H,m), 2.83-3.33 (1H,m), 3.78(6H,s), 4.79-5.05(1H,m), 6.68(1H,d,J=6 Hz), 6.84(1H,d,J=8 Hz), 7.00-7.87 (2H,m),8.30(1H,d,J=6 Hz).

EXAMPLE 624-Ethoxy-9-(5-methoxybenzimidazole-2-yl)sulfinyl-3-methyl-2,3-cycloheptenopyridine

In a stream of argon, 794 mg (2.07 mmol) of4-ethoxy-9-(5-methoxybenzimidazole-2-yl)thio-3-methyl-2,3-cycloheptenopyridineis dissolved in 25 ml of methylene chloride, 424 mg (1.97 mmol) ofm-chloroperbenzoic acid dissolved in 13 ml of methylene chloride isadded dropwise thereto with stirring at -12° C., and the mixture isstirred at the temperature for 5 minutes. After completion of thereaction, the reaction mixture is poured into a saturated sodiumhydrogen carbonate solution, followed by extraction with methylenechloride. The methylene chloride layer is washed with water andsaturated saline and dried over anhydrous magnesium sulfate, and thesolvent is distilled away under reduced pressure. The resulting residueis crystallized from methylene chloride-ether to obtain 427 mg (51.6%)of4-ethoxy-9-(5-methoxybenzimidazole-2-yl)sulfinyl-3-methyl-2,3-cycloheptenopyridineas pale yellow powder having a melting point of 152° to 154° C.

IRν max(KBr): 2976, 2932, 1626, 1462, 1442, 1404, 1204, 1184, 1154,1054, 1024, 998, 962, 818, 808 cm⁻¹.

NMR(CDCl₃)δ: 1.00-2.65(8H,m), 1.31(3H,t,J =7 Hz), 2.19(3H,s), 2.73-3.66(2H,m), 3.82(3H,s), 4.86-5.23 (1H,m), 6.55(1H,bs), 6.85(1H, bd,J=9 Hz),7.62(1H,bd,J=9 Hz), 8.20(1H,bs).

EXAMPLE 639-[1-(Benzyloxycarbonyl)benzimidazole-2-yl]sulfinyl-4-methoxy-2,3-cycloheptenopyridine

In a stream of argon, 630 mg (1.37 mmol) of9-[1-(benzyloxycarbonyl)benzimidazole-2-yl]thio-4-methoxy-2,3-cycloheptenopyridineis dissolved in 20 ml of methylene chloride, and under stirring at -20°C. to -10° C., 281 mg (1.30 mmol) of m-chloroperbenzoic acid dissolvedin 10 ml of methylene chloride is dropwise added little by little. Afterstirring at -10° C. to 0° C. for 50 minutes, the reaction mixture ispoured into a saturated aqueous sodium hydrogen carbonate solution,followed by extraction with methylene chloride. The methylene chloridelayer is washed with water and saturated saline ad dried over anhydrousmagnesium sulfate, and the solvent is distilled away under reducedpressure. The residue is crystallized from methylenechloride-ether-hexane and further recrystallized from methylenechloride-ether to obtain 171 mg (27.9%) of9-[1-(benzyloxycarbonyl)benzimidazole-2-yl]sulfinyl-4-methoxy-2,3-cycloheptenopyridineas colorless powder having a melting point of 91° to 95° C.

IRν max(KBr): 2928, 2852, 1752, 1734, 1580, 1474, 1440, 1396, 1332,1304, 1284, 1256, 1204, 1118, 1074 cm⁻¹.

NMR(CDCl₃)δ: 1.62-2.67(7H,m), 3.06-3.45 (1H,m), 3.77(3H,s), 4.85(1H,d,J=10.5 Hz), 5.43(2H,s), 6.55 (1H,d,J=7.5 Hz), 7.06-7.53(6H,m),7.56-8.06(2H,m), 7.99(1H,d,J=7.5 Hz).

EXAMPLE 64 9-[1-(t-Butoxycarbonylmethoxymethyl)benzimidazole-22-yl]sulfinyl-4-methoxy-2,3-cycloheptenopyridine

In a stream of argon, 469 mg (1.00 mmol) of 9-[1-(tbutoxycarbonylmethoxymethyl)benzimidazole-2-yl]-thio-4-methoxy-2,3-cycloheptenopyridineis dissolved in 20 ml of methylene chloride, 205 mg (0.95 mmol) ofm-chloroperbenzoic acid dissolved in 10 ml of methylene chloride isadded dropwise little by little under stirring at -20° C. to -10° C.,and the mixture is stirred at that temperature for 1 hour. The reactionmixture is poured into a saturated aqueous sodium hydrogen carbonatesolution, followed by extraction with methylene chloride. The methylenechloride layer is washed with water and saturated saline and dried overanhydrous magnesium sulfate, and the solvent is distilled away underreduced pressure. The residue is purified by activated alumina columnchromatography (ethyl acetate-hexane 1:2→1:1 →ethyl acetate) to obtain165 mg (35.2%) of9-[1-(t-butoxycarbonylmethoxymethyl)benzimidazole-2-yl]sulfinyl-4-methoxy-2,3-cycloheptenopyridine.

IRν max(KBr): 2976, 2932, 1742, 1580, 1474, 1450, 1368, 1284, 1238,1156, 1054 cm⁻¹.

NMR(CDCl₃)δ: 1.45(9H,s), 1.63-2.76(7H,m), 3.06-3.42(1H,m), 3.81(3H,s),4.97(1H,d,J=9.0 Hz), 5.13(2H,s), 5.67(1H,d,J=13.5 Hz), 5.91(1H,d,J =13.5Hz), 6.65(1H,d,J=7.5 Hz), 7.04-7.90(4H,m), 8.22(1H,d,J=7.5 Hz).

EXAMPLE 659-[1-(Ethoxycarbonyl)benzimidazole-2-yl]sulfinyl-4-methoxy-2,3-cycloheptenopyridine

In a stream of argon, 227 mg (0.62 mmol) of9-(benzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridine sodiumsalt is dissolved in 15 ml of dry THF, 0.09 ml (0.93 mmol) of ethylchlorocarbonate is added dropwise under stirring at room temperature,and the mixture is stirred for 1 hour. After the reaction, the solventis distilled away under reduced pressure, the residue is dissolved inmethylene chloride, and the solution is washed with water. The methylenechloride layer is dried over anhydrous magnesium sulfate, the solvent isdistilled away under reduced pressure, and the solid residue isrecrystallized from methylene chloride-ether to obtain 194 mg (75.2%) of9[(1-ethoxycarbonyl)benzimidazole-2-yl]sulfinyl-4-methoxy-2,3-cycloheptenopyridineas colorless powder having a melting point of 183° to 185° C.

IRν max(KBr): 2924, 1756, 1578, 1472, 1450, 1428, 1400, 1376, 1342,1316, 1296, 1282, 1260, 1186, 1020, 756, 738 cm⁻¹.

NMR(CDCl₃)δ: 1.08-2.73(7H,m), 1.43(3H,t,J=7 Hz), 3.13-3.50(1H,m), 3.78(3H,s), 4.53(2H,q,J=7 Hz), 4.93 (1H,d,J=9 Hz), 6.58(1H,d,J=5 Hz),7.20-7.53(2H,m), 7.81-8.02 (2H,m), 8.08(1H,d,J=5 Hz).

EXAMPLE 669-(Benzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridine sodiumsalt

In a stream of argon, 100g (527 mmol) of 28% sodium methylate and 530 mlof dry methylene chloride are placed in a 5 1 three-necked flask, andunder stirring at room temperature, 120 g (350 mmol) of9-(benzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridine isadded, and the mixture is stirred for 2 hours.

Then, ether is added dropwise, and after 30 minutes stirring at roomtempeature, the mixture is stirred at -30° C. for 2 hours. The depositedcrystals are collected by filtration, and after removal of the methanolinsoluble matters and acetone insoluble matters, recrystallized frommethylene chloride-ether to obtain 107 g (83.9%) of9-(benzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridine sodiumsalt as colorless powder having a melting point of 167° to 175° C.(decomposition).

IRν max(KBr): 3372, 3048, 2972, 2928, 2856, 1580, 1474, 1298, 1270,1090, 1052, 1036, 820, 800, 744 cm⁻¹.

NMR(CDCl₃ -DMSO-d₆)δ: 1.00-2.63(7H,m), 2.95-3.34(1H,m), 3.82(3H,s),4.75(1H,d,J=6 Hz), 6.65(1H,d,J=5 Hz), 6.85-7.10(2H,m), 7.40-7.65 (2H,m),8.23(1H,d,J=5 Hz).

EXAMPLE 679-(Benzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridinepotassium salt

In a stream of argon, 342 mg (1.00 mmol) of9-(benzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cyclheptenopyridine isdissolved in 5 ml of dry methylene chloride, 137 mg (1.20 mmol) ofpotassium t-butoxide is added, and the mixture is stirred at roomtemperature for 16.5 hours.

Then, ether is added dropwise, followed by stirring at room temperaturefor 2 hours. The deposited crystals are collected by filtration, andrecrystallized from chloroform and then from methanol-ether to obtain110 mg (28.9%) of9-(benzimidazole-2-yl)sulfinyl-4-methoxy-2,3-cycloheptenopyridinepotassium salt as colorless powder having a melting point of 159° to163° C. (decomposition).

IRν max(KBr): 3400, 2924, 1580, 1476, 1460, 1428, 1376, 1308, 1288,1264, 1082, 1058, 1030, 802, 742 cm⁻¹.

NMR(CDCl₃ -DMSO-d₆)δ: 1.00-2.73(7H,m), 3.00-3.45(1H,m), 3.79(3H,s),4.81(1H,bs), 6.52(1H,d,J=5 Hz), 6.77-7.06(2H,m), 7.32-7.63(2H,m),(2H,m), 8.13(1H,d,J=5 Hz).

EXAMPLE 689-[pyrido[2,3-d]imidazole-2-yl]sulfinyl-2,3-cycloheptenopyridine

In a stream of argon, 700 g (2.36 mmol) of9-[pyriod[2,3-d]imidazole-2-yl]thio-2,3-cyclheptenopyridine is dissolvedin 25 ml of methylene chloride, 358 mg (2.25 mmol) of m-chloroperbenzoicacid dissolved in 4 ml of methylene chloride is added dropwise withstirring at -18° C., and the mixture is stirred at the same temperaturefor 5 minutes. After completion of the reaction, the reaction mixture ispoured into a saturated aqueous sodium hydrogen carbonate solution andextracted with methylene chloride. The methylene chloride layer iswashed with water and saturated saline and dried over anhydrousmagnesium sulfate, and the solvent is distilled away under reducedpressure. The resulting residue is crystallized from methylenechloride-ether to obtain 252 mg (34.2%) of9-[pyrido[2,3-d]imidazole-2-yl]sulfinyl-2,3-cycloheptenopyridine ascolorless crystals having a melting point of 133.5° to 135° C.

IR0max(KBr): 2960, 1635, 1455, 1295, 1064, 821 cm⁻¹.

NMR(CDCl₃): 1.10-2.28(5H,m), 2.28-3.20 (3H,m), 4.56-4.86(1H,m),6.83-7.60(3H,m), 7.90-8.40(2H,m), 8.70-8.40(1H,m).

The compounds shown in Table-5 are obtained in the same manner as inExamples 61 to 68.

    TABLE 5      ##STR22##       Example      Melting point   No. R R.sup.1 R.sup.2 R.sup.3 A (yield)     IRνcm.sup.-1 NMR(CDCl.sub.3)δ       69 H H 5-OCH.sub.3 H CH Colorless powder (KBr) 3116, 3092, 2940, 1626, 1     .15-2.33(6H, m), 2.53-2.84(2H, m), 3.79       (55.7%) 1454, 1438 1198,     1026, 820, (3H, s), 4.84-5.08(1H, m), 6.47-7.78       132-134° C.      (5H, m), 8.35(1H, d, J=5Hz) 70 H H 5-NO.sub.2 H CH Yellow powder (KBr)     2935, 2858, 1620, 1522, 0.73-3.18(8H, m), 4.73-5.18(1H, m),     (48.8%) 1434, 1342, 1040, 812, 738, 6.94-7.73(3H, m), 7.96-8.57(3H, m)         129-134° C. 71 H H 5-Cl H CH Yellowish amor- (KBr) 3072,     2932, 2852, 1615, 1.03-2.46(6H, m), 2.62-2.93(2H, m),       phous powder     1578, 1454, 1434, 1042, 920, 4.70-5.04(1H, m), 6.86-7.87(5H, m),     (40.0%) 806, 8.31(1H, d, J=5Hz)       -- 72 H H 5-F H CH Colorless     powder (KBr) 3064, 2858, 1626, 1578, 1.13-2.40(6H, m), 2.45-3.09(2H, m),           (33.0%) 1490, 1454, 1434, 1348, 1108, 4.85-5.13(1H, m), 6.68-7.90(5     H, m),       155-156° C. 1028, 968, 802, 748, 8.35(1H, d, J=6Hz)     73 H H 5-CH.sub.3 H CH Yellowish amor- (KBr) 3056, 2982, 2856, 1578,     1.23-2.15(6H, m), 2.40(3H, s), 2.43-2.96       phous powder 1454, 1434,     1038, 968, 804, (2H, m), 4.83-5.18(1H, m), 6.78-7.83       (64.8%) 754,     (5H, m), 8.34(1H, d, J=5Hz)       -- 74 H H 5-CF.sub.3 H CH Palely     yellow (KBr) 2932, 2856, 1434, 1330, 1.13-2.35(6H, m), 2.46-3.03(2H, m),           amorphous powser 1162, 1120, 1048, 814, 4.83-5.21(1H, m), 6.90-8.10     (5H, m),       (34.4%)  8.27(1H, d, J=5Hz)       -- 75 H OCH.sub.3 H H     CH Yellowish powder (KBr) 3068, 2972, 2932, 2852, 1.07-2.74(6H, m),     2.95-3.40(2H, m), 3.82       (63.5%) 1580, 1476, 1454, 1430, 1286, (3H,     s), 4.73-4.98(1H, m), 6.69(1H, d, J=6       147-150° C. 1270,     1086, 1054, 996, 746, Hz), 7.06-7.92(4H, m), 8.30(1H, d, J=6Hz) 76 H     OCH.sub.3 5-F H CH Colorless powder (KBr) 3068, 2976, 2940, 2856,     1.00-2.55(6H, m), 2.92-3.30(2H, m), 3.79       (46.3%) 1620, 1580, 1476,     1430, 1284, (3H, s), 4.73-5.05(1H, m), 6.68(1H, d, J=5       161-163.degr     ee. C. 1276, 1088, 1058, 994, 812, Hz), 6.77-7.76(3H, m), 8.28(1H, d,     J=5Hz) 77 H OEt H H CH Palely brown (KBr) 3430, 3064, 2976, 2928,     1.43(3H, t, J=7.5Hz), 1.60-2.65(7H, m),       powder (52.4%) 1580, 1466,     1430, 1312, 1286, 3.03-3.36(1H, m), 4.03(2H, q, J=7.5Hz),       112-118.d     egree. C. 1268, 1052, 744, 4.93(1H, d, J=6Hz), 6.65(1H, d, J=7.5Hz)      (decomposed)  7.09-7.70(4H, m), 8.26(1H, d, J=7.5Hz) 78 H O.sup.nBu H H     CH Colorless needle (KBr) 3450, 3056, 2960, 2936, 0.96(3H, t, J=7.5Hz),     1.13-2.56(11H, m),       crystal (58.0%) 1588, 1466, 1428, 1310, 1290,     3.05-3.34(1H, m), 3.95(2H, t, J=7.5Hz),       150-154° C. 1268,     1046, 4.80(1H, d, J=9Hz), 6.67(1H, d, J=7.5Hz),       (decomposed)  7.10     -7.93(4H, m), 8.26(1H, d, 7.5Hz),      79 H     ##STR23##      H H CH Colorless pris-matic crystal(66.2%)162-165° C. (KBr)     3500, 3040, 2936, 2856,1576, 1506, 1466, 1428, 1268,1242, 1206, 1008,     1.12-2.70(7H, m), 2.33(3H, s), 3.10-3.53(1H, m), 4.89(1H, d, J=7.5Hz),     6.50(1H, d,J=7.5Hz), 6.76(2H, d, J=10.5Hz), 6.96-7.93(4H, m), 7.16(2H,     6(2H, d, J=10.5Hz),8.20(1H, d, J=10.5Hz)      80 H     ##STR24##      H H CH Palely brownprismatic crystal(59.8%)138-140°      C.(decomposed) (KBr) 3456, 3012, 2944, 2872,2808, 1580, 1472, 1452,     1428,1412, 1298, 1266, 1038, 1008, 0.20-0.76(4H, m), 1.05-2.66(8H, m),     3.10-3.52(1H, m), 3.12(2H, d, J=7.5Hz), 4.75(1H, d, J=10.5Hz), 6.65(1H,     d, J=7.5Hz)7. 06-7.95(4H, m), 8.25(1H, d, J=7.5Hz)      81 H     ##STR25##      H H CH Colorless powder(55.2%)147-148° C.(decomposed) (KBr)     3432, 3068, 2972, 2932,1578, 1464, 1432, 1290, 1268,1052, 1006, 1.13-2.63     (7H, m), 3.10-3.48(1H, m),3.68-4.43(5H, m), 4.75(1H, d, J=10.5Hz),6.73(1H     , d, J=7.5Hz), 8.20(1H, d, J=7.5Hz)  82 H OCH.sub.3 H CH.sub.2      OCOCH.sub.3 CH Colorless powder (KBr) 2932, 1752, 1580, 1466, 1.23-2.81(     7H, m), 2.10(3H, s), 3.06-3.46       (10.5%) 1440, 1364, 1350, 1284,     1252, (1H, m), 3.81(3H, s), 5.11(1H, d, J=9Hz),       141-144° C.     1206, 1088, 1050, 1024, 6.46, 6.76(1H×2, d, J=13.5Hz), 6.63(1H, d,            J=7.5Hz), 7.10-7.93(4H, m), 8.15(1H, d,         J=7.5Hz) 83 H     OCH.sub.3 H CH.sub.2 OCH.sub.3 CH Colorless powder (KBr) 2920, 1580,     1476, 1434, 1.23-2.80(7H, m), 3.10-3.53(1H, m),       (25.9%) 1334,     1318, 1286, 1262, 1110, 3.41(3H, s), 3.82(3H, s), 5.02-5.29     132-136° C. 1092, 1044, (1H, m), 5.75, 6.06(1H×2, d,     J=13.5Hz),         6.65(1H, d, J=7.5Hz), 7.13-7.93(4H, m),     8.16(1H, d, J=7.5Hz) 84 H OCH.sub.3 H CH.sub.2 OEt CH Colorless powder     (KBr) 2928, 2852, 1580, 1474, 1.19(3H, t, J=9Hz), 1.48-2.83(7H, m),      (51.8%) 1438, 1340, 1092, 1052, 3.08-3.43(1H, m), 3.62(2H, q, J=9Hz),         112-114° C.  3.08(3H, s), 5.03-5.33(1H, m), 5.76, 5.98      (1H×2, d, J=13.5Hz), 6.65(1H, d, J=7.5Hz),         7.14-7.90(4H,     m), 8.16(1H, d, J=7.5Hz) 85 H OCH.sub.3 H CH.sub.2 O(CH.sub.2).sub.2     OCH.sub.3 CH Colorless amor- (KBr) 2924, 2852, 1588, 1464, 1.34-2.80(8H,     m), 3.30(3H, s), 3.47(2H,       phous powder 1438, 1336, 1316, 1284,     1134, t, J=6Hz), 3.73(2H, t, J=6Hz), 3.80(3H,       (47.7%) 1090, s),     5.12(1H, d, J=9Hz), 5.84, 6.13(1H×2,       45-49° C.  d,     J=13.5Hz), 6.65(1H, d, J=7.5Hz), 7.13-         7.92(4H, m), 8.13(1H, d,     J=7.5Hz) 86 H OCH.sub.3 H COO(CH.sub.2).sub.2 OCH.sub.3 CH Colorless     powder (KBr) 2920, 1746, 1580, 1474, 1.53-2.75(8H, m), 3.33(3H, s),     3.66(2H,       (35.7%) 1448, 1380, 1330, 1284, 1256, t, J=6Hz), 3.76(3H,     s), 4.57(2H, t, J=6Hz)       176-179° C. 1206, 1078, 4.89(1H, d,     J=12Hz), 6.56(1H, d, J=7.5Hz),         7.08-8.15(4H, m), 8.09(1H, d,     J=7.5Hz) 87 H OCH.sub.3 H CH.sub.2 COOEt CH Colorless powder (KBr) 2932,     2852, 1744, 1580, 1.26(3H, t, J=9Hz), 1.60-2.76(7H, m),       (24.2%)     1476, 1448, 1308, 1222, 1048, 3.06-3.37(1H, m), 3.81(3H, s), 4.23(2H,        --  q, J=9Hz), 4.94.5.17(1H, m), 5.13, 5.78         (1H×2, d,     J=22.5Hz), 6.65(1H, d, J=7.5Hz),         7.04-7.86(4H, m), 8.20(1H, d,     J=7.5Hz) 88 3-CH.sub.3 OCH.sub.3 H H CH Colorless powder (KBr) 3448,     3070, 2932, 1470, 1.38-2.70(7H, m), 2.23(3H, s), 2.87-3.26       (64.2%)     1455, 1434, 1398, 1266, 1056, (1H, m), 3.55(3H, s), 4.86(1H, d, J=9Hz),          166-168° C. 1011, 7.03-7.84(4H, m), 8.20(1H, s)     (decomposed) 89 3-CH.sub.3 OCH.sub.3 H Na.sup.+ CH Colorless powder     (KBr) 3432, 2932, 1562, 1470, *1       (67.7%) 1450, 1380, 1290, 1270,     1056, 1.33-2.26(7H, m), 2.10(3H, s), 2.84-3.25       189-195° C.     1006, (1H, m), 3.63(3H, s), 4.60-4.85(1H, m),       (decomposed)     6.76-7.10(2H, m), 7.30-7.63(2H, m),         8.02(1H, s) 90 H OCH.sub.2     CH.sub.2 OCH.sub.3 F H CH Colorless powder (KBr) 3036, 2988, 2936, 2880,     1.00-2.65(7H, m), 2.97-3.30(1H, m), 3.39       (51.7%) 2788, 1576, 1476,     1448, 1430, (3H, s), 3.58-3.81(2H, m), 3.93-4.21(3H,       141-143.degree     . C. 1406, 1276, 1132, 1106, 1086, m), 4.70-5.01(1H, m), 6.69(1H, d,     J=6Hz),        1064, 1036, 1016, 994, 966, 6.70-7.80(3H, m), 8.24(1H, d,     J=6Hz)        836, 806, 796, 91 H OCH.sub.3 5,6-OCH.sub.3 H CH Colorless     powder (KBr) 3064, 2976, 2932, 2856, 1.00-3.30(8H, m), 3.80(3H, s),     3.87(6H,       (71.8%) 1580, 1490, 1478, 1434, 1326, s), 4.85-5.12(1H,     m), 6.65-6.80(2H, d, J=       176-178° C. 1284, 1240, 1194, 1180,     1140, 6Hz), 7.06- 7.30(1H, m), 8.29(1H, d, J=       (decomposed) 1054,     1008, 998, 830, 6Hz) 92 H OCH.sub.2 CF.sub.3 H H CH Colorless powder     (KBr) 3432, 3304, 2932, 1580, *2       (39.2%) 1472, 1454, 1436, 1370,     1318, 1.36-3.40(8H, m), 4.47(2H, m), 4.73-4.95       -- 1294, 1266,     1160, 1142, 1102, (1H, m), 6.77(1H, d, J=6Hz), 7.16-7.37        1044,     976, (2H, m), 7.53-7.81(2H, m), 8.44(1H, d, J=         6Hz) 93 H     OCH.sub.2 CHCH.sub.2 H H CH Yellow amorphous (KBr) 2952, 2920, 2872,     1580, 1.00-3.33(8H, m), 4.35-4.63(2H, m),       powder 1472, 1426, 1310,     1298, 1282, 4.67-5.00(1H, m), 5.07-5.56(2H, m), 5.70-       (37.7%)     1040, 1014, 994, 750, 746, 6.20(1H, m), 6.57(1H, d, J=7Hz), 6.92-     --  7.33(2H, m), 7.36-8.07(3H, m), 8.18(1H,         d, J=7Hz) 94 H     OCH.sub.2 CH.sub.2 OCH.sub.3 H H CH Colorless powder (KBr) 2924, 2876,     2852, 1580, 1.00-2.70(8H, m), 3.39(3H, s), 3.60-3.82       (42.0%) 1472,     1452, 1428, 1270, 1082, (2H, m), 3.95-4.21(2H, m), 4.78-5.03       --     1052, 998,750, (1H, m), 6.66(1H, d, J=6Hz), 7.07-7.34         (2H, m),     7.36-7.67(2H, m), 8.24(1H, d, J=         6Hz) 95 H OCH.sub.2 CH.sub.2 OH     H H CH Yellow amorphous (KBr) 3416, 2928, 2856, 1580, 1.00-3.60(8H, m),     3.80-4.33(4H, m),       powder 1472, 1450, 1312, 1290, 1270, 4.66-5.00(1H     , m), 6.68(1H, d, J=6Hz),       (24.3%) 1240, 1136, 1078, 1054, 946,     7.06-7.83(4H, m), 8.23(1H, d, J=6Hz)       -- 904, 800, 746,  96 H      ##STR26##      H H CH Paley orangepowder(34.3%)135-137° C. (KBr) 3064, 2968,     2936, 2856,1736, 1580, 1452, 1432, 1286,1268, 1250, 1230, 1092, 1058, 100     6, 744, 1.06-3.43(8H, m), 2.08(3H, s), 4.05-4.28(2H, m), 4.33-4.53(2H,     m), 4.69-4.96(1H, m), 4.68(1H, d, J=5Hz), 7.10-8.00(4H, m), 8 .28(1H, d,     J=5Hz)  97 H O(CH.sub.2).sub.3 OCH.sub.3 H H CH Colorless powder (KBr)     3064, 3012, 2932, 2872, 0.99-2.65(10H, m), 3.31(3H, s), 3.50(2H,     (28.4%) 2808, 1580, 1478, 1458, 1430, t, J=6Hz), 4.06(2H, t, J=6Hz,     6Hz),       135-136.5°      C. 1412, 1310, 1288, 1270, 1192, 4.63-4.93(1H, m), 6.70(1H, d, J=6Hz),           1138, 1118, 1096, 1082, 1054, 7.03-7.70(4H, m), 8.27(1H, d, J=6Hz)            1006, 816, 800, 750, 98 H O(CH.sub.2).sub.2 OCH.sub.2 Ph H H CH     Yellow amorphous (KBr) 3060, 2924, 2856, 1578, 1.06-3.59(8H, m),     3.67-3.93(2H, m), 3.98-       powder 1470, 1452, 1428, 1310, 1286,     4.25(2H, m), 4.57(2H, s), 4.66-4.99(1H,       (89.3%) 1268, 1128, 1088,     1036, 1002, m), 6.67(1H, d, J=6Hz), 7.00-7.71(9H, m),       -- 800, 742,     696, 8.25(1H, d, J=6Hz) 99 H O(CH.sub.2).sub.2 OPh H H CH Colorless     powder (KBr) 3064, 2820, 1580, 1458, 1.00-3.35(8H, m), 4.27(3H, s),     4.66-4.92       (39.7%) 1478, 1454, 1432, 1272, 1244, (1H, m), 6.67(1H,     d, J=6Hz), 6.78-7.71       144-145° C. 1086, 1064, 1006, 814,     800, (9H, m), 8.22(1H, d, J=6Hz)        756, 744 100 H O(CH.sub.2).sub.2     OCH.sub.2 Py H H CH Yellow amorphous (KBr) 3060, 2928, 2856, 1578,     1.00-3.45(8H, m), 3.77-4.03(2H, m),       powder 1474, 1450, 1432, 1356,     1286, 4.03-4.31(2H, m), 4.69(2H, s), 4.75-5.01       (40.0%) 1268, 1238,     1134, 1088, 1046, (1H, m), 6.68(1H, d, J=6Hz), 7.00-7.80       -- 1002,     800, 746, (7H, m), 8.25(1H, d, J=6Hz), 8.52(1H, d,         J=6Hz)  101 H      ##STR27##      H H CH  Colorless powder(53.3%)140-141° C. (KBr) 3064, 3020,     2932, 2864,2800, 1692, 1580, 1458, 1426,1288, 1086, 998, 746, 1.00-2.70(1     2H, m), 2.93-3.80(4H, m),3.85-4.33(2H, m), 4.65-5.00(1H, m),6.66(1H, d,     J=5Hz), 6.98-8.06(4H, m),8.26(1H, d, J=5Hz)  102 H OCH.sub.2 CF.sub.2     CHF.sub.2 H Na.sup.+ CH Colorless powder (KBr) 3388, 3052, 2932, 2860,     *1       (72.7%) 1580, 1472, 1454, 1378, 1292, 1.16-3.50(8H, m),     4.16-5.00(3H, m),       169-171.5° C. 1270, 1248, 1202, 1122,     1020, 6.13-6.37(1H, m), 6.60-7.10(3H, m),        802, 746 7.30-7.69(2H,     m), 8.23(1H, d, J=6Hz) 103 H OCH.sub.3 H CH.sub.2 OH CH Colorless powder     (KBr) 3256, 3060, 2924, 2852, 1.14-3.50(8H, m), 3.84(3H, s),     (42.7%) 1580, 1474, 1432, 1340, 1314, 5.07-5.33(1H, m), 5.66(1H, d,     J=12Hz),       120-122° C. 1282, 1244, 1136, 1054, 814, 6.17(1H,     d, J=12Hz), 6.72(1H, d, J=6Hz)        742, 7.13-7.90(4H, m), 8.06-8.40(1H     , m), 104 3-CH.sub.3 OCH.sub.2 CF.sub.2 CF.sub.2 H 5-F H CH Colorless     powder (KBr) 3034, 2932, 2854, 1497, *2       (44.8%) 1470, 1455, 1434,     1413, 1263 1.13-3.29(8H, m), 2.21(3H, s), 3.75-4.24       163-165°      C. 1221, 1197, 1137, 1110, 1080, (2H, m), 4.68-5.02(1H, m), 5.36-6.76          1059, 1002, 966, 954, 843, (1H, m), 6.76-7.83(3H, m), 8.17(1H, s)          810, 105 3-CH.sub.3 OCH.sub.3 5-OCH.sub.3 H CH Colorless powder     (KBr) 3064, 3000, 2924, 2852, 1.10-3.20(8H, m), 2.17(3H, s), 3.41(3H,        (60.4%) 1626, 1454, 1438, 1406, 1396, s), 3.80(3H, s), 4.86-5.26(1H,     m),       163-165° C. 1204, 1184, 1054, 1022, 1008 6.51(1H, bs),     6.70-7.30(2H, m), 7.46-       (decomposed) 996, 962, 820, 808, 7.71(1H,     d, J=10Hz), 8.18(1H, s) 106 H OCH.sub.2 CH.sub.2 OCH.sub.3 5-CH.sub.3 H     CH Palely orange (neat) 3048, 2976, 2932, 2852, 1.05-3.30(8H, m),     2.44(3H, s), 3.40(3H,       powder 1578, 1452, 1430, 1334, 1308, s),     3.55-3.85(2H, m), 3.90-4.23(2H, m),       (42.7%) 1288, 1274, 1196,     1134, 1086, 4.60-4.96(1H, m), 6.70(1H, d, J=6Hz),       118-121°     C. 1060, 1008, 966, 802, 6.86-7.28(2H, m), 7.36-7.80(1H, m),     8.28(1H, d, J=6Hz) 107 3-CH.sub.3 OCH.sub.2 CF.sub.2 CF.sub.2      H 5-OCH.sub.3 H CH Colorless powder (KBr) 3080, 3048, 3004, 2936,     1.07-2.03(6H, m), 2.19(3H, s), 2.26-3.15       (38.8%) 2904, 1624, 1460,     1406, 1200, (2H, m), 3.40-4.02(2H, m), 3.81(3H, s),       166-168°      C. 1178, 1126, 1112, 1094, 1070, 5.03-7.30(4H, m), 7.61(1H, d, J=10Hz),            996, 964, 816, 8.26(1H, s) 108 H OCH.sub.3 5-CH.sub.3 H CH     Colorless powder (KBr) 2974, 2926, 1581, 1479, 1.20-2.70(7H, m),     2.68(3H, s), 3.21-3.69       (39.5%) 1452, 1434, 1284, 1086, 1053 (1H,     m), 4.19(3H, s), 5.20-5.45(1H, d, J=       155- 156° C. 1008,     822, 11Hz), 7.27-7.43(1H, d, J=7Hz), 7.62-         7.90(2H, m), 8.15-8.52     (1H, m), 9.06-9.18         (1H, d, J=7Hz) 109 H OCH.sub.2 CH.sub.2     OCH.sub.3 H COOCH.sub.2 CH.sub.2 OCH.sub.3 CH Colorless powder (KBr     2926, 1746, 1578, 1449, 1.10-2.66(6H, m), 3.36(3H, s), 3.40(3H,     (16.7%) 1419, 1374, 1323, 1305, 1287, s), 3.55-3.83(4H, m), 3.96-4.20(2H,      m),       108-110° C. 1254, 1206, 1119, 1077, 996, 4.40-4.71(2H,     m), 4.91(1H, d, J=10Hz),        840, 756, 747, 6.58(1H, d, J=6Hz),     7.15-7.51(2H, m),         7.66-8.03(2H, m), 8.08(1H, d, J=6Hz) 110 H     OCH.sub.3 H H N Colorless powder (KBr) 2920, 1583, 1479, 1291, 1.19-2.70(     7H, m), 3.12-3.50(1H, m),       (44.0%) 1266, 1059, 800, 3.79(3H, s),     4.56-4.80(1H, d, J=10Hz),       139-140° C.  6.59-6.75(1H, d,     J=6Hz), 7.10-7.33(1H,         dd, J=6Hz), 8.00-8.36(2H, m), 8.36-8.65          (1H, d, J=5Hz) 111 H OCH.sub.2 Ph H H CH Colorless powder (KBr)     3064, 2932, 1578, 1474, 1.00-2.66(7H, m), 3.08-3.43 (1H, m),     (62.5%) 1462, 1454, 1432, 1284, 1268, 4.84(1H, d, J=7Hz), 5.04(2H, s),     6.73(1H,       155-158.5° C. 1044, 1024, 1010, 798, 748, d,     J=5Hz), 7.10-7.93(4H, m), 7.33(5H, s),       (decomposed) 424, 8.27(1H,     d, J=5Hz) 112 H OCH.sub.2 CF.sub.2 CF.sub.3 H H CH Colorless powder     (KBr) 3320, 2940, 1578, 1470, 1.04-2.66(7H, m), 2.95-3.40(1H, m),     (60.8%) 1454, 1436, 1372, 1316, 1294, 4.38(2H, t, J=12Hz), 4.90(1H, d,     J=6Hz),       161-162° C. 1266, 1212, 1196, 1142, 1102, 6.63(1H,     d, J=5Hz), 7.10-7.92(4H, m),       (decomposed) 1046, 946, 748, 8.32(1H,     d, J=5Hz) 113 H OCH.sub.2 CF.sub.2 CF.sub.2 H H H CH Colorless powder     (KBr) 3320, 2932, 1580, 1472, 1.15- 3.52(8H, m), 4.33(2H, t, J=12Hz),        (65.4%) 1454, 1432, 1372, 1316, 1292, 4.92(1H, d, J=6Hz), 5.28, 5.93,     6.52(1H, t       150-154° C. 1270, 1240, 1222, 1206, 1118,     ×3, J=3Hz), 6.65(1H, d, J=6Hz), 7.10-7.90        1068, 1046, 946,     820, 748, 4H, m), 8.32(1H, d, J=6Hz), 11.70(1H, br) 114 H SCH.sub.2     CH.sub.2 CH.sub.3 H H CH Colorless powder (KBr) 3068, 2960, 2928, 2868,     1.06(3H, t, J=7Hz), 1.25-3.67(10H, m),       (45.2%) 1564, 1452, 1432,     1406, 1266, 2.87(2H, t, J=7Hz), 4.92(1H, d, J=6Hz),       133-134°      C. 1024, 800, 766, 744, 6.96(1H, d, J=5Hz), 7.05-7.97(4H, m),     (decomposed)  8.24(1H, d, J=5Hz)      115 H     ##STR28##      H H CH Brown powder(18.4%)143-145° C.(decomposed) (KBr) 3456,     3064, 2932, 2856,1630, 1578, 1452, 1430, 12661114, 1024, 1006, 990, 744, *     21.10- 3.40(12H, m), 3.70-4.00(4H, m),4.63-4.85(1H, m), 6.87(1H, d,     J=6Hz),7.18-7.80(4H, m), 8.29(1H, d, J=6Hz)      116 H OCH.sub.3 H     ##STR29##      CH Paley brownpowder(23.7%)138-141° C. (KBr) 2912, 2848, 1734,     1578,1282, 1254, 1088, 1064, 10481024, 738, 714 1.10-3.45(8H, m),     3.74(3H, s), 5.23-5.52(1H, m), 6.47(1H, d, J=6Hz), 6.73, 6.91(1H×2,      d, J=11Hz), 7.86(1H, d, J=6Hz),7.11-8.18(9H, m),  117 H Cl 5-OCH.sub.3     H CH Colorless powder (KBr) 3224, 3080, 3004, 2936, 1.02-2.78(7H, m),     2.93-3.41(1H, m), 3.79       (44.2%) 1626, 1560, 1504, 1454, 1406, (3H,     s), 5.05(1H, br), 6.56-7.75(4H, m),       153-155° C. 1304, 1204,     1176, 1150, 1030, 8.24(1H, br)       (decomposed) 966, 834, 804, 118     3-CH.sub.3 OCH.sub.2 CH.sub.2 OCH.sub.3 H H CH Colorless powder (KBr)     3070, 2926, 1470, 1455, 1.25-2.90(7H, m), 3.20-3.58(1H, m), 2.41     (77.1%) 1407, 1266, 1059, 1011, 747, (3H, s), 3.71(3H, s), 3.96(4H, s),     5.48-       148-150° C.  5.72(1H, d, J=10Hz), 7.62-8.07(4H, m),           8.38-8.68(1H, m), 9.00(1H, s) 119 3-CH.sub.3 OCH.sub.2 CH.sub.2     OCH.sub.3 5-F H CH Colorless powder (KBr) 2932, 1460, 1137, 1005,     1.20-2.69(7H, m), 2.21(3H, s), 2.90-3.21       (69.5%)  (1H, m),     3.65(3H, s), 3.45-3.78(4H, s),       146-147° C.  4.90-5.16(1H,     m), 6.50-7.82(3H, m), 8.16         (1H,s) 120 3-CH.sub.3 OCH.sub.3 5-F H     CH Colorless powder (KBr) 3070, 2932, 1470, 1455, 1.17-2.70(7H, m),     2.21(3H, s), 2.83-3.17       (50.7%) 1011, 996, (1H, m), 3.47(3H, s),     4.90-5.17(1H, m),       160-161.5° C.  6.48-7.76(3H, m), 8.17(1H,     s) 121 H OCH.sub.2 CF.sub.3 H Na CH Colorless powder (KBr) 3420, 1580,     1472, 1454, 1.00-3.60(6H, m), 4.40-4.96(3H, m),       (77.6%) 1376,     1290, 1264, 1166, 1090, 6.70-7.08(3H, m), 7.33-7.65(2H, m),       --     1016, 972, 744, 8.26(1H, d, J=6Hz) 122 3-CH.sub.3 SCH.sub.2 CH.sub.2     CH.sub.3 H H CH Colorless powder (KBr) 2962, 2926, 1434, 1410, 0.80-1.05(     3H, t, J=7Hz), 1.10-2.10(8H, m)       (71.4%) 1380, 1266, 999, 798, 744,     2.21-2.50(2H, t, J=8Hz), 2.44(3H, s),       158-159°      C.  2.53-2.93(1H, m), 3.40-3.71(1H, m),         4.98-5.18(1H, d,     J=11Hz), 7.03-7.33(3H,         m), 7.62-7.84(1H, m), 8.28(1H,s) 123 H     OCH.sub.2 CH.sub.2 OCH.sub.3 H H N Brown amorphous (KBr) 2920, 1580,     1452, 1270, 1.05-1.60(2H, m), 1.62-2.75(4H, m), 3.43       powder 1123,     1059, (3H, s), 3.62-3.90(2H, m), 3.95-4.28(2H,       (77.1%)  m),     4.50-4.72(1H, d, J=10Hz), 6.56-6.80       97-99° C.  (1H, m),     7.07-7.30(1H, m), 7.80-8.52(3H,         m) 124 3-CH.sub.3 H H H N Yellow     amorphous (KBr) 2926, 1404, 1269, 1050, 1.32-3.15(8H, m), 2.20(3H, s),     4.56-4.78       powder 957, 909, 888, 804, 774, (1H, d, J=9Hz), 7.23(3H,     m), 7.80-8.26       (42.4%)  (2H, m), 8.40-8.60(6H, d, J=6Hz)     99-102° C. 125 3-CH.sub.3 OCH.sub.3 H H N Palely yellow (KBr)     2943, 1600, 1477, 1440, 1.30-2.75(7H, m), 1.69(3H, s), 2.21(3H,     powder 1410, 1268, 1059, 817, s), 3.06-3.21(1H, m), 4.60-4.80(1H, d,       (78.8%)  J=10Hz), 7.15-7.36(1H, t), 8.03-8.16       138-140° C.      (1H, d, J=7Hz), 8.16(1H, s), 8.43-8.60         (1H, d, J=6Hz) 126     3-CH.sub.3 OCH.sub.2 CF.sub.2 CF.sub.2 H H H N Colorless powder (KBr)     2935, 1590, 1454, 1407, 1.30-2.75(7H, m), 2.19(3H, s), 3.06-3.21     (83.7%) 1269, 1195, 1107, 1051, (1H, m), 3.86-4.25(3H, t, J=12Hz), 5.30-           118-119° C.  6.70(2H, m), 7.13-7.40(1H, m), 8.00-8.28       (2H, m), 8.45-8.60(1H, d, J=5Hz) 127 H OCH.sub.3 H SO.sub.2 CH.sub.3     CH Colorless powde (KBr) 2988, 1584, 1476, 1434, 1.00-3.50(8H, m),     3.53(3H, s), 3.76(3H,       (11.8%) 1358, 1286, 1250, 1234, 1170, s),     5.39(1H, d, J=10Hz), 6.51(1H, d, 6Hz),       159-161° C. 1046,     974, 812, 772, 538, 518, 7.13-7.53(2H, m), 7.58-8.00(2H, m),     7.85(1H, d, J=6Hz)     In the table     *1 CDCl.sub.3 -- acetoned.sub.6     *2 CDCl.sub.3 -- DMSOd.sub.6

We claim:
 1. A cycloheptenopyridine derivative of the formula ##STR30##wherein R represents a hydrogen atom or lower alkyl group; R¹ representsa hydrogen atom, halogen atom, lower cycloalkoxy group, amido group,substituted phenoxy group, substituted benzyloxy group, lower alkoxygroup optionally containing halogen atom(s), nitro group, hydroxylgroup, lower alkenyloxy group, lower alkylthio group, or a group --NR⁴R⁵ wherein R⁴ and R⁵ may be the same or different and each represents ahydrogen atom or lower alkyl group, or R⁴ and R⁵ mutually combinetogether with the nitrogen atom adjacent thereto to form a 5- or 6-membered heterocyclic group; R² represents a hydrogen atom, halogenatom, lower alkyl group optionally containing a halogen atom, loweralkoxy group optionally containing a halogen atom, hydroxyl group, acylgroup, lower alkoxycarbonyl group, nitro group or amino group; R³represents a hydrogen atom, a lower alkyl group, lower alkoxymethylgroup, lower alkylcarbonyl group, lower alkoxycarbonyl group, carbamoylgroup, lower alkylcarbamoyl group, lower alkylcarbonylmethyl group,lower alkoxycarbonylmethyl group, lower acyloxymethyl group, loweralkylsulfonyl group, or physiologically acceptable protective groupeliminatable in an acid medium or under physiological conditions; nrepresents 0 or 1; and A represents a methine carbon or nitrogen atom ora pharmaceutically acceptable salt thereof.
 2. An antiulcer compositionwhich comprises an effective amount of a cycloheptenopyridine derivativeof claim 1 or a pharmaceutically acceptable salt thereof, as aneffective ingredient and a pharmaceutically acceptable carrier therefor.